%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Marilena P. Etna, Alessandro Sinigaglia, Angela Grassi, Elena Giacomini, Alessandra Romagnoli, Manuela Pardini, Martina Severa, Melania Cruciani, Fabiana Rizzo, Eleni Anastasiadou, Barbara Di Camillo, Luisa Barzon, Gian Maria Fimia, Riccardo Manganelli, Eliana M. Coccia
Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells
www.plospathogens.org
www.plospathogens.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 14 0 R/Contents 15 0 R/TrimBox[0 0 612 792]>>
endobj
14 0 obj
[16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R]
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref001)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref002)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref003)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref004)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref005)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref006)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref007)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref007)>>
endobj
24 0 obj
<>/Border[0 0 0]/A 25 0 R>>
endobj
25 0 obj
<>
endobj
15 0 obj
[26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R]
endobj
26 0 obj
<>stream
q
0.955 g
0 w
199.9998 707.4 m
575.9997 707.4 l
575.9997 481.4005 l
199.9998 481.4005 l
f*
0.83 0.64 0.02 0 k
517.1528 393.9024 m
521.915 393.9024 l
h
f*
239.1874 341.915 m
243.9496 341.915 l
h
f*
435.1181 263.9055 m
439.8236 263.9055 l
h
f*
444.3024 263.9055 m
449.0646 263.9055 l
h
f*
532.3465 224.9008 m
537.1087 224.9008 l
h
f*
400.8189 185.8961 m
405.5811 185.8961 l
h
f*
444.9827 120.926 m
449.7449 120.926 l
h
f*
220.5921 81.9213 m
225.3543 81.9213 l
h
f*
0 g
1 j
1 J
11.9999 0 0 11.9999 209.9905 689.3858 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Author)Tj
3.137 0 Td
(summary)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 209.9905 671.4141 cm
BT
/F13 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()47()3()7()13()4()6()-4()11()2( )-9(\n)12()12()]TJ
6.3212 0 Td
[()7()14()4()2( )20()1()4(\r)4()7()10(\n)-4()]TJ
/F8 1 Tf
4.8018 0 Td
(\(Mtb\))Tj
2.5965 0 Td
(is)Tj
0.8504 0 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(most)Tj
2.2054 0 Td
(successful)Tj
4.1612 0 Td
(pathogens)Tj
4.303 0 Td
(in)Tj
1.0375 0 Td
(human)Tj
3.0727 0 Td
(his-)Tj
-33.5336 -1.3039 Td
(tory)Tj
1.8538 0 Td
(and)Tj
1.7291 0 Td
(remains)Tj
3.4469 0 Td
(the)Tj
1.4684 0 Td
(second)Tj
3.0103 0 Td
(leading)Tj
3.1295 0 Td
(cause)Tj
2.3924 0 Td
(of)Tj
1.0148 0 Td
(death)Tj
2.4321 0 Td
(from)Tj
2.2053 0 Td
(an)Tj
1.2019 0 Td
(infectious)Tj
4.1329 0 Td
(agent)Tj
2.3868 0 Td
(worldwide.)Tj
-30.4042 -1.2982 Td
(The)Tj
1.7858 0 Td
(major)Tj
2.6078 0 Td
(reason)Tj
2.863 0 Td
(of)Tj
1.0148 0 Td
(Mtb)Tj
1.9162 0 Td
(success)Tj
3.1011 0 Td
(relies)Tj
2.313 0 Td
(on)Tj
1.2756 0 Td
(its)Tj
1.1452 0 Td
(ability)Tj
2.6986 0 Td
(to)Tj
1.0261 0 Td
(evade)Tj
2.4831 0 Td
(host)Tj
1.9106 0 Td
(immunity.)Tj
4.4504 0 Td
(Autophagy,)Tj
-30.5913 -1.2983 Td
(a)Tj
0.6576 0 Td
(cellular)Tj
3.1351 0 Td
(mechanism)Tj
4.8472 0 Td
(involved)Tj
3.6453 0 Td
(in)Tj
1.0375 0 Td
(intracellular)Tj
5.057 0 Td
(pathogen)Tj
3.9458 0 Td
(elimination,)Tj
5.0683 0 Td
(is)Tj
0.8504 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(path-)Tj
-32.4281 -1.2983 Td
(ways)Tj
2.1543 0 Td
(hijacked)Tj
3.5773 0 Td
(by)Tj
1.1792 0 Td
(Mtb)Tj
1.9219 0 Td
(to)Tj
1.0261 0 Td
(elude)Tj
2.3641 0 Td
(the)Tj
1.474 0 Td
(control)Tj
3.1181 0 Td
(of)Tj
1.0148 0 Td
(dendritic)Tj
3.8777 0 Td
(cells)Tj
1.9162 0 Td
(\(DC\),)Tj
2.5285 0 Td
(major)Tj
2.6079 0 Td
(cellular)Tj
3.1408 0 Td
(effectors)Tj
-31.9009 -1.3039 Td
(of)Tj
1.0091 0 Td
(immune)Tj
3.6226 0 Td
(response.)Tj
3.9515 0 Td
(Recently,)Tj
3.8834 0 Td
(it)Tj
0.7824 0 Td
(has)Tj
1.5364 0 Td
(become)Tj
3.3165 0 Td
(clear)Tj
2.1146 0 Td
(that)Tj
1.7745 0 Td
(Mtb)Tj
1.9105 0 Td
(infection)Tj
3.7871 0 Td
(not)Tj
1.5704 0 Td
(only)Tj
1.9729 0 Td
(alters)Tj
2.3471 0 Td
(cellu-)Tj
-33.579 -1.2982 Td
(lar)Tj
1.2699 0 Td
(gene)Tj
2.0806 0 Td
(expression,)Tj
4.6941 0 Td
(but)Tj
1.5534 0 Td
(also)Tj
1.7688 0 Td
(controls)Tj
3.4809 0 Td
(the)Tj
1.4684 0 Td
(level)Tj
2.0182 0 Td
(of)Tj
1.0148 0 Td
(small)Tj
2.3244 0 Td
(RNA)Tj
2.262 0 Td
(molecules,)Tj
4.4221 0 Td
(namely)Tj
3.1464 0 Td
(micro-)Tj
-31.504 -1.2983 Td
(RNAs)Tj
2.6248 0 Td
(\(miRNAs\),)Tj
4.6148 0 Td
(which)Tj
2.6475 0 Td
(function)Tj
3.6284 0 Td
(as)Tj
1.0148 0 Td
(negative)Tj
3.5376 0 Td
(regulators)Tj
4.2236 0 Td
(of)Tj
1.0148 0 Td
(mRNA)Tj
3.084 0 Td
(translation)Tj
4.5354 0 Td
(into)Tj
-30.9257 -1.3039 Td
(protein.)Tj
3.3788 0 Td
(In)Tj
1.1112 0 Td
(the)Tj
1.4683 0 Td
(present)Tj
3.1635 0 Td
(study,)Tj
2.6135 0 Td
(we)Tj
1.3266 0 Td
(observed)Tj
3.7984 0 Td
(that)Tj
1.7802 0 Td
(the)Tj
1.4683 0 Td
(infection)Tj
3.7927 0 Td
(of)Tj
1.0148 0 Td
(human)Tj
3.0728 0 Td
(DC)Tj
1.6214 0 Td
(with)Tj
1.9956 0 Td
(Mtb)Tj
1.9218 0 Td
(leads)Tj
-33.5279 -1.2983 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.6519 0 Td
(strong)Tj
2.7723 0 Td
(induction)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(host)Tj
1.9105 0 Td
(miR-155,)Tj
3.9345 0 Td
(a)Tj
0.6519 0 Td
(critical)Tj
2.9537 0 Td
(regulator)Tj
3.8608 0 Td
(of)Tj
1.0148 0 Td
(host)Tj
1.9162 0 Td
(immune)Tj
3.6226 0 Td
(response.)Tj
3.9629 0 Td
(By)Tj
-33.4316 -1.2983 Td
(mean)Tj
2.4491 0 Td
(of)Tj
1.0148 0 Td
(miR-155)Tj
3.702 0 Td
(induction,)Tj
4.3596 0 Td
(Mtb)Tj
1.9219 0 Td
(reduces)Tj
3.2769 0 Td
(Atg3)Tj
2.1429 0 Td
(protein)Tj
3.1521 0 Td
(content,)Tj
3.4923 0 Td
(a)Tj
0.6576 0 Td
(crucial)Tj
2.914 0 Td
(enzyme)Tj
3.2995 0 Td
(needed)Tj
-32.3827 -1.3039 Td
(for)Tj
1.3889 0 Td
(the)Tj
1.4684 0 Td
(initial)Tj
2.5455 0 Td
(phase)Tj
2.4831 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(autophagic)Tj
4.6204 0 Td
(process.)Tj
3.4073 0 Td
(Interestingly,)Tj
5.4935 0 Td
(miR-155)Tj
3.7077 0 Td
(silencing)Tj
3.77 0 Td
(during)Tj
-31.3736 -1.2982 Td
(Mtb)Tj
1.9162 0 Td
(infection)Tj
3.7927 0 Td
(restores)Tj
3.3392 0 Td
(Atg3)Tj
2.143 0 Td
(level)Tj
2.0125 0 Td
(and)Tj
1.7292 0 Td
(rescues)Tj
3.1124 0 Td
(autophagy.)Tj
4.6148 0 Td
(These)Tj
2.5625 0 Td
(findings)Tj
3.4979 0 Td
(contribute)Tj
4.388 0 Td
(to)Tj
1.0261 0 Td
(bet-)Tj
-34.1345 -1.2983 Td
(ter)Tj
1.3152 0 Td
(elucidate)Tj
3.7927 0 Td
(Mtb-triggered)Tj
5.8791 0 Td
(escape)Tj
2.8006 0 Td
(mechanisms)Tj
5.21 0 Td
(and)Tj
1.7291 0 Td
(highlight)Tj
3.8098 0 Td
(the)Tj
1.474 0 Td
(importance)Tj
4.8302 0 Td
(to)Tj
1.0205 0 Td
(develop)Tj
-31.8612 -1.3039 Td
(host-directed)Tj
5.5275 0 Td
(therapies)Tj
3.8437 0 Td
(to)Tj
1.0262 0 Td
(combat)Tj
3.2088 0 Td
(tuberculosis)Tj
5.0399 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(autophagy)Tj
4.388 0 Td
(boosting.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 438.0094 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 421.0015 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(As)Tj
1.2642 0 Td
(estimated)Tj
4.0705 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(2016)Tj
2.1203 0 Td
(global)Tj
2.6306 0 Td
(WHO)Tj
2.6985 0 Td
(report,)Tj
/F13 1 Tf
2.931 0 Td
[()47()3()7()13()4()6()-4()11()2( )-9(\n)12()12()]TJ
6.3213 0 Td
[()7()14()4()2( )20()1()4(\r)4()7()10(\n)-4()]TJ
/F8 1 Tf
4.8018 0 Td
(\(Mtb\),)Tj
2.8233 0 Td
(the)Tj
1.4683 0 Td
(causative)Tj
-33.783 -1.2982 Td
(agent)Tj
2.3867 0 Td
(of)Tj
1.0148 0 Td
(tuberculosis)Tj
5.04 0 Td
(\(TB\))Tj
2.0919 0 Td
(in)Tj
1.0375 0 Td
(humans,)Tj
3.6623 0 Td
(infects)Tj
2.8347 0 Td
(approximately)Tj
5.9754 0 Td
(10)Tj
1.1678 0 Td
(million)Tj
3.1238 0 Td
(people)Tj
2.8516 0 Td
(each)Tj
2.0296 0 Td
(year,)Tj
2.1317 0 Td
(mak-)Tj
-35.3478 -1.3039 Td
(ing)Tj
1.5023 0 Td
(TB)Tj
1.406 0 Td
(the)Tj
1.474 0 Td
(second)Tj
3.0104 0 Td
(leading)Tj
3.1294 0 Td
(cause)Tj
2.3924 0 Td
(of)Tj
1.0148 0 Td
(death)Tj
2.4321 0 Td
(from)Tj
2.2054 0 Td
(an)Tj
1.2018 0 Td
(infectious)Tj
4.1329 0 Td
(disease)Tj
3.0161 0 Td
(worldwide)Tj
4.456 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
-30.1774 -1.2983 Td
(The)Tj
1.7801 0 Td
(success)Tj
3.0954 0 Td
(of)Tj
1.0092 0 Td
(Mtb)Tj
1.9162 0 Td
(principally)Tj
4.507 0 Td
(relies)Tj
2.3074 0 Td
(on)Tj
1.2699 0 Td
(its)Tj
1.1452 0 Td
(ability)Tj
2.6872 0 Td
(to)Tj
1.0205 0 Td
(perfectly)Tj
3.6623 0 Td
(adapt)Tj
2.4265 0 Td
(to)Tj
1.0204 0 Td
(the)Tj
1.4627 0 Td
(host,)Tj
2.1373 0 Td
(by)Tj
1.1736 0 Td
(establish-)Tj
-33.8171 -1.2983 Td
(ing)Tj
1.5023 0 Td
(latent)Tj
2.4661 0 Td
(infection)Tj
3.7928 0 Td
(and)Tj
1.7291 0 Td
(evading)Tj
3.3392 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.474 0 Td
(control)Tj
3.1181 0 Td
(driven)Tj
2.812 0 Td
(by)Tj
1.1848 0 Td
(immune)Tj
3.6284 0 Td
(system.)Tj
3.1634 0 Td
(In)Tj
1.1055 0 Td
(this)Tj
1.6724 0 Td
(scenario,)Tj
-33.1934 -1.3039 Td
(both)Tj
2.0579 0 Td
(innate)Tj
2.7382 0 Td
(and)Tj
1.7348 0 Td
(adaptive)Tj
3.5773 0 Td
(immune)Tj
3.6227 0 Td
(responses)Tj
4.0932 0 Td
(are)Tj
1.4513 0 Td
(required)Tj
3.6397 0 Td
(to)Tj
1.0261 0 Td
(control)Tj
3.1181 0 Td
(TB)Tj
1.4117 0 Td
(progression)Tj
4.9209 0 Td
(and)Tj
1.7291 0 Td
(path-)Tj
-35.121 -1.2982 Td
(ogenesis)Tj
3.5773 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
-2.3811 -1.2983 Td
(In)Tj
1.1111 0 Td
(particular,)Tj
4.337 0 Td
(the)Tj
1.4684 0 Td
(interaction)Tj
4.6091 0 Td
(of)Tj
1.0148 0 Td
(mycobacteria)Tj
5.5842 0 Td
(with)Tj
1.9956 0 Td
(antigen-presenting)Tj
7.7782 0 Td
(cells)Tj
1.9218 0 Td
(\(APC\))Tj
2.8063 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.652 0 Td
(key)Tj
-35.3251 -1.2983 Td
(feature)Tj
2.9876 0 Td
(in)Tj
1.0319 0 Td
(the)Tj
1.4683 0 Td
(pathogenesis)Tj
5.3574 0 Td
(of)Tj
1.0148 0 Td
(TB)Tj
1.4117 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(outcome)Tj
3.7247 0 Td
(of)Tj
1.0205 0 Td
(this)Tj
1.6724 0 Td
(interaction)Tj
4.6035 0 Td
(is)Tj
0.8504 0 Td
(pivotal)Tj
2.9423 0 Td
(in)Tj
1.0375 0 Td
(determining)Tj
-32.3204 -1.3039 Td
(whether)Tj
3.4752 0 Td
(immunity)Tj
4.2236 0 Td
(or)Tj
1.0998 0 Td
(disease)Tj
3.0161 0 Td
(would)Tj
2.7099 0 Td
(ensue.)Tj
2.7326 0 Td
(Human)Tj
3.3165 0 Td
(and)Tj
1.7291 0 Td
(murine)Tj
3.1805 0 Td
(macrophages)Tj
5.5048 0 Td
(and)Tj
1.7291 0 Td
(dendritic)Tj
-32.7172 -1.2983 Td
(cells)Tj
1.9218 0 Td
(\(DC\))Tj
2.2961 0 Td
(were)Tj
2.1259 0 Td
(shown)Tj
2.846 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(infected)Tj
3.4186 0 Td
(by)Tj
1.1792 0 Td
(mycobacteria)Tj
5.5842 0 Td
(and,)Tj
1.9559 0 Td
(in)Tj
1.0375 0 Td
(turn,)Tj
2.1883 0 Td
(to)Tj
1.0261 0 Td
(produce)Tj
3.5206 0 Td
(a)Tj
0.652 0 Td
(specific)Tj
-31.9292 -1.2982 Td
(immune)Tj
3.6226 0 Td
(response.)Tj
3.9628 0 Td
(As)Tj
1.2643 0 Td
(professional)Tj
5.0513 0 Td
(APC,)Tj
2.3527 0 Td
(DC)Tj
1.6157 0 Td
(display)Tj
3.0274 0 Td
(indeed)Tj
2.9424 0 Td
(an)Tj
1.2019 0 Td
(extraordinary)Tj
5.6919 0 Td
(capacity)Tj
3.4752 0 Td
(to)Tj
1.0262 0 Td
(stim-)Tj
-35.2344 -1.3039 Td
(ulate)Tj
2.1486 0 Td
(na)Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(ve)Tj
2.3357 0 Td
(T)Tj
0.8334 0 Td
(cells)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(initiate)Tj
3.0217 0 Td
(primary)Tj
3.4583 0 Td
(immune)Tj
3.6226 0 Td
(responses)Tj
4.0989 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(4)Tj
0 g
(].)Tj
-23.2326 -1.2983 Td
(Once)Tj
2.364 0 Td
(in)Tj
1.0375 0 Td
(contact)Tj
3.1521 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.474 0 Td
(pathogen,)Tj
4.1669 0 Td
(immature)Tj
4.1783 0 Td
(DC)Tj
1.6214 0 Td
(undergo)Tj
3.5886 0 Td
(maturation,)Tj
4.9549 0 Td
(modifying)Tj
4.3597 0 Td
(their)Tj
-34.0892 -1.2983 Td
(phenotypic)Tj
4.7054 0 Td
(features)Tj
3.3449 0 Td
(and)Tj
1.7291 0 Td
(producing)Tj
4.3767 0 Td
(several)Tj
2.9367 0 Td
(pro-inflammatory)Tj
7.455 0 Td
(and)Tj
1.7291 0 Td
(regulatory)Tj
4.32 0 Td
(cytokines)Tj
3.9968 0 Td
(with)Tj
-34.5937 -1.3039 Td
(the)Tj
1.4683 0 Td
(ability)Tj
2.6929 0 Td
(to)Tj
1.0261 0 Td
(tune)Tj
2.0183 0 Td
(the)Tj
1.4683 0 Td
(immune)Tj
3.6283 0 Td
(response)Tj
3.7304 0 Td
(by)Tj
1.1849 0 Td
(acting)Tj
2.6532 0 Td
(on)Tj
1.2756 0 Td
(different)Tj
3.6566 0 Td
(cellular)Tj
3.1408 0 Td
(populations)Tj
4.9493 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
1.6044 0 Td
(These)Tj
-34.4974 -1.2982 Td
(events)Tj
2.7269 0 Td
(result)Tj
2.4491 0 Td
(into)Tj
1.8425 0 Td
(a)Tj
0.652 0 Td
(fine)Tj
1.7461 0 Td
(control)Tj
3.1237 0 Td
(exerted)Tj
3.1521 0 Td
(at)Tj
0.9525 0 Td
(transcriptional,)Tj
6.3382 0 Td
(post-transcriptional)Tj
8.1467 0 Td
(and)Tj
1.7348 0 Td
(post-trans-)Tj
-32.8646 -1.2983 Td
(lational)Tj
3.1974 0 Td
(level.)Tj
2.2394 0 Td
(In)Tj
1.1111 0 Td
(turn,)Tj
2.194 0 Td
(host)Tj
1.9106 0 Td
(factors,)Tj
3.1294 0 Td
(utilized)Tj
3.1918 0 Td
(by)Tj
1.1792 0 Td
(mycobacterial)Tj
5.8337 0 Td
(molecules,)Tj
4.422 0 Td
(play)Tj
1.8708 0 Td
(an)Tj
1.2019 0 Td
(important)Tj
4.2803 0 Td
(role)Tj
-35.7616 -1.3039 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(regulation)Tj
4.3086 0 Td
(and)Tj
1.7291 0 Td
(progression)Tj
4.9209 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(infection)Tj
3.7927 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
-18.5441 -1.2983 Td
(In)Tj
1.1111 0 Td
(light)Tj
2.024 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2563 0 Td
(observations,)Tj
5.4822 0 Td
(it)Tj
0.788 0 Td
(is)Tj
0.8447 0 Td
(conceivable)Tj
4.8813 0 Td
(that)Tj
1.7801 0 Td
(Mtb)Tj
1.9162 0 Td
(infection)Tj
3.7928 0 Td
(might)Tj
2.5965 0 Td
(not)Tj
1.576 0 Td
(only)Tj
1.9729 0 Td
(alter)Tj
1.9956 0 Td
(cellu-)Tj
-35.2287 -1.2983 Td
(lar)Tj
1.2699 0 Td
(gene)Tj
2.0806 0 Td
(expression)Tj
4.4674 0 Td
(but)Tj
1.5533 0 Td
(also)Tj
1.7688 0 Td
(control)Tj
3.1181 0 Td
(important)Tj
4.2803 0 Td
(regulators)Tj
4.2293 0 Td
(of)Tj
1.0148 0 Td
(mRNA)Tj
3.0784 0 Td
(translation,)Tj
4.7622 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(micro-)Tj
-34.6958 -1.2982 Td
(RNAs)Tj
2.6191 0 Td
(\(miRNAs\).)Tj
4.6205 0 Td
(As)Tj
1.2642 0 Td
(a)Tj
0.652 0 Td
(class)Tj
2.0466 0 Td
(of)Tj
1.0148 0 Td
(small)Tj
2.3244 0 Td
(non-coding)Tj
4.9152 0 Td
(RNAs,)Tj
2.846 0 Td
(miRNAs)Tj
3.7134 0 Td
(are)Tj
1.4456 0 Td
(highly)Tj
2.7099 0 Td
(conserved)Tj
4.2633 0 Td
(within)Tj
-34.435 -1.3039 Td
(eukaryotic)Tj
4.422 0 Td
(species)Tj
2.999 0 Td
(and)Tj
1.7291 0 Td
(function)Tj
3.6284 0 Td
(as)Tj
1.0147 0 Td
(key)Tj
1.5931 0 Td
(regulators)Tj
4.2293 0 Td
(of)Tj
1.0148 0 Td
(gene)Tj
2.0806 0 Td
(expression)Tj
4.4617 0 Td
(by)Tj
1.1849 0 Td
(post-transcriptional)Tj
-28.3576 -1.2983 Td
(targeting)Tj
3.7927 0 Td
(of)Tj
1.0148 0 Td
(mRNAs)Tj
3.4412 0 Td
(for)Tj
1.3833 0 Td
(translation)Tj
4.5354 0 Td
(arrest)Tj
2.4775 0 Td
(or)Tj
1.0998 0 Td
(for)Tj
1.389 0 Td
(degradation)Tj
5.0229 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.5988 0 Td
(These)Tj
2.5682 0 Td
(effects)Tj
2.7269 0 Td
(are)Tj
1.4456 0 Td
(mediated)Tj
3.9458 0 Td
(by)Tj
-36.4419 -1.2983 Td
(imperfect)Tj
4.0535 0 Td
(binding)Tj
3.3505 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(miRNA-recognition)Tj
8.3282 0 Td
(elements)Tj
3.7644 0 Td
(within)Tj
2.8119 0 Td
(the)Tj
1.4683 0 Td
(3')Tj
0.9128 0 Td
(untranslated)Tj
5.2384 0 Td
(region)Tj
-32.4111 -1.3039 Td
(\(UTR\))Tj
2.8686 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(target)Tj
2.5115 0 Td
(mRNAs)Tj
3.4412 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(miRNA)Tj
3.3505 0 Td
(`seed')Tj
2.3981 0 Td
(region)Tj
2.8007 0 Td
(located)Tj
3.0784 0 Td
(between)Tj
3.5319 0 Td
(residues)Tj
3.4809 0 Td
(28)Tj
1.6895 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(5')Tj
-36.5496 -1.2983 Td
(end)Tj
1.7177 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 144.5669 23.6976 re
W* n
q
144.5102 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 428.0881 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(ATG3)Tj
2.8063 0 Td
(impairme)Tj
4.0394 0 Td
(nt)Tj
1.0417 0 Td
(by)Tj
1.2544 0 Td
(Mtb-induc)Tj
4.3157 0 Td
(ed)Tj
1.3111 0 Td
(miR-155)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
102.0472 34.9228 m
256.1953 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Pathogens)Tj
4.9252 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://)Tj
2.9552 0 Td
(doi.org/10.13)Tj
5.7331 0 Td
(71/journal.p)Tj
5.1236 0 Td
(pat.1006)Tj
3.8198 0 Td
(790)Tj
0 g
2.6362 0 Td
(January)Tj
3.7134 0 Td
(4,)Tj
1.0418 0 Td
(2018)Tj
31.8616 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(30)Tj
/F10 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(Education,)Tj
4.1031 0 Td
(Universities)Tj
4.5284 0 Td
(and)Tj
1.5874 0 Td
(Research)Tj
3.6993 0 Td
(and)Tj
1.5874 0 Td
(grant)Tj
-15.5056 -1.3748 Td
(FILAS-RU-)Tj
3.9897 0 Td
(2014-1036)Tj
4.3158 0 Td
(\(to)Tj
1.2544 0 Td
(EMC\))Tj
2.2819 0 Td
(from)Tj
2.0126 0 Td
(Lazio)Tj
2.1402 0 Td
(Region.)Tj
-15.9946 -1.3749 Td
(The)Tj
1.5874 0 Td
(funders)Tj
3.0472 0 Td
(had)Tj
1.5874 0 Td
(no)Tj
1.1693 0 Td
(role)Tj
1.6158 0 Td
(in)Tj
0.8858 0 Td
(study)Tj
2.2607 0 Td
(design,)Tj
2.9055 0 Td
(data)Tj
-15.0591 -1.3748 Td
(collection)Tj
3.7417 0 Td
(and)Tj
1.5874 0 Td
(analysis)Tj
2.9623 0 Td
(,)Tj
0.4464 0 Td
(decision)Tj
3.2882 0 Td
(to)Tj
0.9496 0 Td
(publish,)Tj
3.1465 0 Td
(or)Tj
-16.1221 -1.3748 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F9 1 Tf
-6.7606 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F10 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
27 0 obj
<>stream
endstream
endobj
28 0 obj
<>stream
endstream
endobj
29 0 obj
<>stream
endstream
endobj
30 0 obj
<>stream
endstream
endobj
31 0 obj
<>stream
endstream
endobj
32 0 obj
<>stream
endstream
endobj
33 0 obj
<>stream
endstream
endobj
34 0 obj
<>stream
BT
10.3394 75.0903 Td
(exist)Tj
ET
Q
endstream
endobj
35 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 38 0 R/Contents 39 0 R/TrimBox[0 0 612 792]>>
endobj
38 0 obj
[40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R]
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref007)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref008)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref009)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref010)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref011)>>
endobj
45 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref012)>>
endobj
46 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref013)>>
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g001)>>
endobj
48 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.t001)>>
endobj
49 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g001)>>
endobj
50 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g001)>>
endobj
51 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref014)>>
endobj
52 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref028)>>
endobj
53 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref014)>>
endobj
54 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.ref028)>>
endobj
55 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g001)>>
endobj
56 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g001)>>
endobj
58 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
59 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
60 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
61 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
62 0 obj
<>/Border[0 0 0]/Dest(Rppat.1006790.g002)>>
endobj
63 0 obj
<>/Border[0 0 0]/A 64 0 R>>
endobj
64 0 obj
<>
endobj
39 0 obj
[65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R]
endobj
65 0 obj
<>stream
q
0.83 0.64 0.02 0 k
362.4945 693.2976 m
367.2567 693.2976 l
h
f*
349.0583 667.3323 m
353.8205 667.3323 l
h
f*
358.2992 667.3323 m
363.0614 667.3323 l
h
f*
535.748 641.3102 m
545.2724 641.3102 l
h
f*
376.3276 602.3055 m
385.852 602.3055 l
h
f*
223.4268 576.3402 m
232.9512 576.3402 l
h
f*
237.3732 576.3402 m
246.8976 576.3402 l
h
f*
294.7465 367.937 m
314.3055 367.937 l
h
f*
390.5008 354.8976 m
419.6976 354.8976 l
h
f*
306.1417 328.9323 m
325.7008 328.9323 l
h
f*
397.2472 289.9276 m
416.8063 289.9276 l
h
f*
319.8614 250.9228 m
329.2724 250.9228 l
h
f*
334.3748 250.9228 m
343.7858 250.9228 l
h
f*
445.3795 237.9402 m
454.7339 237.9402 l
h
f*
459.8929 237.9402 m
469.2472 237.9402 l
h
f*
330.8031 211.9181 m
335.622 211.9181 l
h
f*
354.8409 211.9181 m
366.2929 211.9181 l
h
f*
221.4992 185.8961 m
226.3181 185.8961 l
h
f*
245.537 185.8961 m
256.989 185.8961 l
h
f*
449.9717 172.9134 m
476.0504 172.9134 l
h
f*
467.6598 146.948 m
493.7386 146.948 l
h
f*
557.9717 94.9039 m
570.6142 94.9039 l
h
f*
200.0126 81.9213 m
210.5575 81.9213 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(In)Tj
1.1111 0 Td
(addition)Tj
3.6 0 Td
(to)Tj
1.0205 0 Td
(the)Tj
1.474 0 Td
(known)Tj
3.0047 0 Td
(role)Tj
1.7631 0 Td
(of)Tj
1.0148 0 Td
(miRNAs)Tj
3.7134 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(multi-level)Tj
4.5241 0 Td
(regulation)Tj
4.3086 0 Td
(of)Tj
1.0148 0 Td
(several)Tj
2.931 0 Td
(cell)Tj
1.559 0 Td
(pro-)Tj
-34.7411 -1.3039 Td
(cesses)Tj
2.5738 0 Td
(and)Tj
1.7291 0 Td
(mammalian)Tj
5.04 0 Td
(immune)Tj
3.6283 0 Td
(system)Tj
2.9367 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(],)Tj
1.6044 0 Td
(growing)Tj
3.5262 0 Td
(evidences)Tj
4.0762 0 Td
(show)Tj
2.2961 0 Td
(how)Tj
1.9389 0 Td
(pathogens)Tj
4.3029 0 Td
(pro-)Tj
-33.6526 -1.2982 Td
(foundly)Tj
3.3165 0 Td
(perturb)Tj
3.2371 0 Td
(host)Tj
1.9162 0 Td
(miRNA)Tj
3.3505 0 Td
(expression.)Tj
4.6885 0 Td
(While)Tj
2.6476 0 Td
(the)Tj
1.474 0 Td
(involvement)Tj
5.21 0 Td
(of)Tj
1.0148 0 Td
(miRNAs)Tj
3.7077 0 Td
(in)Tj
1.0375 0 Td
(viral)Tj
1.9955 0 Td
(immune)Tj
-33.5959 -1.2983 Td
(responses)Tj
4.0931 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(well)Tj
1.8198 0 Td
(investigated)Tj
4.989 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(9)Tj
0 g
(],)Tj
1.2586 0 Td
(targeting)Tj
3.7927 0 Td
(of)Tj
1.0148 0 Td
(host)Tj
1.9162 0 Td
(miRNAs)Tj
3.7077 0 Td
(by)Tj
1.1849 0 Td
(bacterial)Tj
3.6226 0 Td
(pathogens)Tj
4.303 0 Td
(is)Tj
-36.629 -1.2983 Td
(less)Tj
1.61 0 Td
(characterized.)Tj
5.7826 0 Td
(Though,)Tj
3.6114 0 Td
(in)Tj
1.0374 0 Td
(recent)Tj
2.7099 0 Td
(years)Tj
2.2621 0 Td
(regulation)Tj
4.3086 0 Td
(of)Tj
1.0148 0 Td
(miRNA)Tj
3.3505 0 Td
(expression)Tj
4.4674 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.1203 0 Td
(recog-)Tj
-33.817 -1.3039 Td
(nized)Tj
2.398 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(molecular)Tj
4.2236 0 Td
(strategy)Tj
3.3222 0 Td
(exploited)Tj
3.9004 0 Td
(by)Tj
1.1792 0 Td
(bacteria)Tj
3.3789 0 Td
(to)Tj
1.0261 0 Td
(manipulate)Tj
4.7339 0 Td
(host)Tj
1.9162 0 Td
(cell)Tj
1.559 0 Td
(pathways)Tj
3.9288 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
2.0806 0 Td
(In)Tj
-35.3137 -1.2982 Td
(particular,)Tj
4.3369 0 Td
(bacteria)Tj
3.3789 0 Td
(may)Tj
1.9275 0 Td
(redirect)Tj
3.3222 0 Td
(several)Tj
2.9367 0 Td
(host)Tj
1.9162 0 Td
(cell)Tj
1.5591 0 Td
(functions)Tj
3.9854 0 Td
(to)Tj
1.0262 0 Td
(sustain)Tj
3.0217 0 Td
(survival)Tj
3.3335 0 Td
(and/or)Tj
2.9367 0 Td
(replica-)Tj
-33.681 -1.2983 Td
(tion.)Tj
2.0635 0 Td
(Most)Tj
2.2791 0 Td
(often,)Tj
2.5115 0 Td
(these)Tj
2.2563 0 Td
(effects)Tj
2.7213 0 Td
(require)Tj
3.1124 0 Td
(the)Tj
1.474 0 Td
(delivery)Tj
3.3845 0 Td
(into)Tj
1.8426 0 Td
(the)Tj
1.4683 0 Td
(host)Tj
1.9162 0 Td
(cytoplasm)Tj
4.2803 0 Td
(of)Tj
1.0148 0 Td
(bacterial)Tj
3.6226 0 Td
(effector)Tj
-33.9474 -1.3039 Td
(proteins)Tj
3.5149 0 Td
(through)Tj
3.4412 0 Td
(specific)Tj
3.1918 0 Td
(secretion)Tj
3.8438 0 Td
(systems)Tj
3.2995 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(].)Tj
2.0749 0 Td
(Among)Tj
3.2485 0 Td
(closely)Tj
2.88 0 Td
(related)Tj
2.9423 0 Td
(bacterial)Tj
3.6283 0 Td
(species,)Tj
3.2202 0 Td
(the)Tj
-35.2854 -1.2983 Td
(mycobacterium)Tj
6.4969 0 Td
(genus)Tj
2.5455 0 Td
(is)Tj
0.8447 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(most)Tj
2.2054 0 Td
(effective)Tj
3.5149 0 Td
(in)Tj
1.0318 0 Td
(inducing)Tj
3.7984 0 Td
(differential)Tj
4.6034 0 Td
(regulation)Tj
4.3087 0 Td
(of)Tj
1.0148 0 Td
(miR-)Tj
-34.5484 -1.2983 Td
(NAs)Tj
2.0012 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(13)Tj
0 g
(].)Tj
-2.5398 -1.3039 Td
(We)Tj
1.61 0 Td
(set)Tj
1.3039 0 Td
(out)Tj
1.5534 0 Td
(to)Tj
1.0262 0 Td
(identify)Tj
3.2938 0 Td
(miRNAs)Tj
3.7077 0 Td
(perturbed)Tj
4.1896 0 Td
(by)Tj
1.1848 0 Td
(Mtb)Tj
1.9163 0 Td
(in)Tj
1.0374 0 Td
(infected)Tj
3.4186 0 Td
(human)Tj
3.0784 0 Td
(primary)Tj
3.4526 0 Td
(DC)Tj
1.6214 0 Td
(and)Tj
-33.5903 -1.2982 Td
(understand)Tj
4.7848 0 Td
(their)Tj
2.109 0 Td
(pathological)Tj
5.0966 0 Td
(relevance.)Tj
4.1953 0 Td
(We)Tj
1.6044 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7801 0 Td
(in)Tj
1.0375 0 Td
(human)Tj
3.0784 0 Td
(DC,)Tj
1.8425 0 Td
(Mtb)Tj
1.9162 0 Td
(induces)Tj
3.2995 0 Td
(miR-155)Tj
-33.3635 -1.2983 Td
(to)Tj
1.0262 0 Td
(negatively)Tj
4.2348 0 Td
(regulate)Tj
3.4072 0 Td
(ATG3,)Tj
2.931 0 Td
(an)Tj
1.2076 0 Td
(E2-ubiquitin-like)Tj
7.1149 0 Td
(conjugating)Tj
4.9606 0 Td
(enzyme)Tj
3.3052 0 Td
(involved)Tj
3.6453 0 Td
(in)Tj
1.0375 0 Td
(autophago-)Tj
-32.8703 -1.3039 Td
(some)Tj
2.33 0 Td
(formation,)Tj
4.4844 0 Td
(thereby)Tj
3.2258 0 Td
(impairing)Tj
4.1782 0 Td
(autophagy.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 482.0031 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
/F15 1 Tf
0 -1.5023 Td
(Identification)Tj
5.9669 0 Td
(of)Tj
1.0678 0 Td
(altered)Tj
3.1228 0 Td
(miRNAs)Tj
3.8221 0 Td
(in)Tj
1.0677 0 Td
(Mtb-infected)Tj
5.6646 0 Td
(DC)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 447.0236 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(To)Tj
1.3379 0 Td
(investigate)Tj
4.4617 0 Td
(whether)Tj
3.4753 0 Td
(Mtb)Tj
1.9162 0 Td
(modulates)Tj
4.3653 0 Td
(the)Tj
1.4683 0 Td
(immune)Tj
3.6283 0 Td
(response)Tj
3.7361 0 Td
(by)Tj
1.1792 0 Td
(acting)Tj
2.6589 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(host)Tj
1.9105 0 Td
(DC)Tj
1.6214 0 Td
(miR-)Tj
-34.503 -1.3039 Td
(Nome,)Tj
2.931 0 Td
(we)Tj
1.3266 0 Td
(perfomed)Tj
4.0988 0 Td
(a)Tj
0.652 0 Td
(global)Tj
2.6249 0 Td
(analysis)Tj
3.3278 0 Td
(of)Tj
1.0148 0 Td
(miRNA)Tj
3.3505 0 Td
(expression)Tj
4.4617 0 Td
(profile)Tj
2.8403 0 Td
(in)Tj
1.0375 0 Td
(human)Tj
3.0784 0 Td
(primary)Tj
3.4583 0 Td
(DC)Tj
-34.2026 -1.2982 Td
(infected)Tj
3.4185 0 Td
(with)Tj
1.9956 0 Td
(Mtb.)Tj
-4.2179 -1.2983 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(prepared)Tj
3.804 0 Td
(from)Tj
2.2111 0 Td
(DC)Tj
1.6157 0 Td
(infected)Tj
3.4242 0 Td
(in)Tj
1.0318 0 Td
(kinetic)Tj
2.948 0 Td
(with)Tj
1.9956 0 Td
(live)Tj
1.6101 0 Td
(H37Rv)Tj
3.016 0 Td
(Mtb)Tj
1.9162 0 Td
(for)Tj
1.389 0 Td
(3,)Tj
0.9184 0 Td
(8)Tj
0.6973 0 Td
(and)Tj
1.7292 0 Td
(24)Tj
1.1735 0 Td
(hours)Tj
-34.6391 -1.3039 Td
(and)Tj
1.7291 0 Td
(microarray)Tj
4.6714 0 Td
(experiment)Tj
4.7792 0 Td
(performed.)Tj
4.6942 0 Td
(A)Tj
0.907 0 Td
(hierarchical)Tj
4.938 0 Td
(clustering)Tj
4.1499 0 Td
(was)Tj
1.7007 0 Td
(constructed)Tj
4.9266 0 Td
(by)Tj
1.1849 0 Td
(consider-)Tj
-33.681 -1.2983 Td
(ing)Tj
1.5023 0 Td
(only)Tj
1.9729 0 Td
(miRNAs)Tj
3.7134 0 Td
(whose)Tj
2.7212 0 Td
(overall)Tj
2.9027 0 Td
(dynamic)Tj
3.6963 0 Td
(profile)Tj
2.8403 0 Td
(was)Tj
1.6951 0 Td
(significantly)Tj
5.091 0 Td
(modulated)Tj
4.5298 0 Td
(in)Tj
1.0374 0 Td
(Mtb)Tj
1.9162 0 Td
(infected)Tj
-33.6186 -1.2982 Td
(versus)Tj
2.7155 0 Td
(uninfected)Tj
4.5014 0 Td
(cells)Tj
1.9162 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\).)Tj
1.2642 0 Td
(The)Tj
1.7801 0 Td
(complete)Tj
3.8778 0 Td
(list)Tj
1.3946 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(68)Tj
1.1735 0 Td
(probes)Tj
2.9083 0 Td
(differentially)Tj
5.3008 0 Td
(expressed,)Tj
4.32 0 Td
(cor-)Tj
-35.4555 -1.304 Td
(responding)Tj
4.7565 0 Td
(to)Tj
1.0261 0 Td
(43)Tj
1.1679 0 Td
(different)Tj
3.6566 0 Td
(miRNAs)Tj
3.7134 0 Td
(is)Tj
0.8447 0 Td
(shown)Tj
2.8516 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Table)Tj
2.4435 0 Td
(1)Tj
0 g
(.)Tj
0.9184 0 Td
(While)Tj
2.6532 0 Td
(only)Tj
1.9786 0 Td
(a)Tj
0.652 0 Td
(few)Tj
1.6157 0 Td
(miRNAs)Tj
3.7077 0 Td
(were)Tj
-33.0177 -1.2982 Td
(down-regulated)Tj
6.5536 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(consequence)Tj
5.3404 0 Td
(of)Tj
1.0148 0 Td
(Mtb)Tj
1.9162 0 Td
(challenge,)Tj
4.1839 0 Td
(the)Tj
1.4684 0 Td
(majority)Tj
3.6283 0 Td
(of)Tj
1.0148 0 Td
(them)Tj
2.2904 0 Td
(were)Tj
2.1259 0 Td
(found)Tj
2.6192 0 Td
(up-regu-)Tj
-33.8227 -1.2983 Td
(lated)Tj
2.1486 0 Td
(in)Tj
1.0375 0 Td
(Mtb-infected)Tj
5.4651 0 Td
(DC)Tj
1.6214 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\).)Tj
1.2585 0 Td
(In)Tj
1.1112 0 Td
(particular,)Tj
4.337 0 Td
(a)Tj
0.652 0 Td
(high)Tj
2.0069 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(miRNAs)Tj
3.7134 0 Td
(showed)Tj
3.2485 0 Td
(a)Tj
0.652 0 Td
(fold)Tj
-33.5053 -1.2983 Td
(change)Tj
3.0387 0 Td
(\(FC\))Tj
2.0919 0 Td
(greater)Tj
3.0104 0 Td
(than)Tj
2.0296 0 Td
(2,)Tj
0.9184 0 Td
(starting)Tj
3.2655 0 Td
(from)Tj
2.2053 0 Td
(3)Tj
0.6974 0 Td
(hours)Tj
2.5114 0 Td
(post)Tj
1.9049 0 Td
(infection)Tj
3.7927 0 Td
(and)Tj
1.7292 0 Td
(in)Tj
1.0374 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(analyzed)Tj
3.702 0 Td
(time-)Tj
-34.5484 -1.3039 Td
(points,)Tj
2.9423 0 Td
(while)Tj
2.3697 0 Td
(only)Tj
1.9786 0 Td
(two)Tj
1.7065 0 Td
(miRNAs,)Tj
3.9344 0 Td
(namely)Tj
3.1465 0 Td
(miR-548m)Tj
4.5297 0 Td
(and)Tj
1.7291 0 Td
(miR-548n,)Tj
4.4787 0 Td
(were)Tj
2.1203 0 Td
(down-regulated)Tj
6.5594 0 Td
(with)Tj
-35.4952 -1.2982 Td
(FC)Tj
1.4116 0 Td
(lower)Tj
2.4491 0 Td
(than)Tj
2.0296 0 Td
(-2)Tj
1.0488 0 Td
(after)Tj
2.0353 0 Td
(24)Tj
1.1678 0 Td
(hours)Tj
2.5172 0 Td
(of)Tj
1.0148 0 Td
(Mtb)Tj
1.9162 0 Td
(infection)Tj
3.7927 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\).)Tj
-20.0068 -1.2983 Td
(To)Tj
-0.01 Tc
1.3322 0 Td
(match)Tj
2.6929 0 Td
(our)Tj
1.5988 0 Td
(miRNA)Tj
3.3165 0 Td
(data)Tj
1.8822 0 Td
(with)Tj
1.9672 0 Td
(those)Tj
2.3017 0 Td
(observed)Tj
3.7417 0 Td
(in)Tj
1.0205 0 Td
(vivo)Tj
1.8709 0 Td
(during)Tj
2.8856 0 Td
(TB)Tj
1.3946 0 Td
(disease,)Tj
3.1918 0 Td
(the)Tj
1.4457 0 Td
(list)Tj
1.3606 0 Td
(of)Tj
0.9978 0 Td
(de-regu-)Tj
-34.1969 -1.3039 Td
(lated)Tj
2.1203 0 Td
(miRNAs)Tj
3.6736 0 Td
(identified)Tj
3.9969 0 Td
(in)Tj
1.0261 0 Td
(infected)Tj
3.3732 0 Td
(DC)Tj
1.6044 0 Td
(was)Tj
1.6838 0 Td
(intersected)Tj
4.5184 0 Td
(with)Tj
1.9729 0 Td
(the)Tj
1.4513 0 Td
(miRNA)Tj
3.3222 0 Td
(profile)Tj
2.7949 0 Td
(found)Tj
2.5909 0 Td
(in)Tj
-34.1289 -1.2983 Td
(patients)Tj
3.3165 0 Td
(affected)Tj
3.2825 0 Td
(by)Tj
1.1678 0 Td
(active)Tj
2.4832 0 Td
(TB)Tj
1.4003 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
3.4979 0 Td
(Interestingly,)Tj
5.4085 0 Td
(among)Tj
2.965 0 Td
(miRNAs)Tj
3.6737 0 Td
(de-regulated)Tj
5.1703 0 Td
(in)Tj
1.0205 0 Td
(TB)Tj
-33.3862 -1.2982 Td
(patients)Tj
3.3165 0 Td
(and)Tj
1.7121 0 Td
(validated)Tj
3.7814 0 Td
(by)Tj
1.1678 0 Td
(real)Tj
1.6725 0 Td
(time)Tj
2.0069 0 Td
(PCR)Tj
2.0466 0 Td
(or)Tj
1.0828 0 Td
(similar)Tj
2.948 0 Td
(techniques)Tj
4.4674 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(],)Tj
3.4979 0 Td
(seven)Tj
2.3981 0 Td
(miRNAsnamely)Tj
-30.098 -1.304 Td
(miR-155,)Tj
3.8834 0 Td
(miR-155)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 273.2598 229.6062 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 277.285 225.9779 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(,)Tj
0.4365 0 Td
(miR-29b-1)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 324.5669 229.6062 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 328.5354 225.9779 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(,)Tj
0.4422 0 Td
(miR-150,)Tj
3.8834 0 Td
(miR-146a,)Tj
4.3086 0 Td
(miR-212)Tj
3.668 0 Td
(and)Tj
1.7121 0 Td
(miR-483-5p)Tj
4.989 0 Td
(were)Tj
2.6079 0 Td
(found)Tj
-34.4634 -1.2982 Td
(altered)Tj
2.9027 0 Td
(in)Tj
1.0205 0 Td
(Mtb-infected)Tj
5.3971 0 Td
(DC)Tj
1.6101 0 Td
(\(Figs)Tj
0.83 0.64 0.02 0 k
2.1485 0 Td
(1)Tj
0 g
0.6917 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7121 0 Td
(2A)Tj
0 g
(\).)Tj
1.9219 0 Td
(Furthermore,)Tj
5.5445 0 Td
(microarray)Tj
4.6091 0 Td
(data)Tj
1.8935 0 Td
(indicated)Tj
3.8835 0 Td
(that)Tj
1.7518 0 Td
(Mtb)Tj
-35.087 -1.2983 Td
(induced)Tj
3.4243 0 Td
(miR-29b-1)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 277.1149 203.6409 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 281.1401 200.0125 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(,)Tj
0.4365 0 Td
(miR-150,)Tj
3.8834 0 Td
(miR-212)Tj
3.668 0 Td
(and)Tj
1.7121 0 Td
(miR-483-5p)Tj
4.989 0 Td
(at)Tj
0.9411 0 Td
(early)Tj
2.1203 0 Td
(time)Tj
2.0012 0 Td
(points)Tj
2.6816 0 Td
(\(3)Tj
1.0261 0 Td
(and)Tj
1.7121 0 Td
(8)Tj
0.6917 0 Td
(hours\))Tj
-33.9758 -1.3039 Td
(\(Figs)Tj
0.83 0.64 0.02 0 k
2.1487 0 Td
(1)Tj
0 g
0.6916 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7122 0 Td
(2A)Tj
0 g
(\).)Tj
1.9218 0 Td
(MiR-150)Tj
3.736 0 Td
(and)Tj
1.7121 0 Td
(miR-212)Tj
3.6623 0 Td
(induction)Tj
4.0819 0 Td
(was)Tj
1.6838 0 Td
(maintained)Tj
4.7281 0 Td
(over)Tj
1.9502 0 Td
(time,)Tj
2.2281 0 Td
(while)Tj
2.3357 0 Td
(24)Tj
1.1622 0 Td
(hour)Tj
-33.7547 -1.2982 Td
(post-infection,)Tj
5.9584 0 Td
(miR-29b-1)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 302.5133 177.6188 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 308.6929 173.9905 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(decreased)Tj
4.0818 0 Td
(and)Tj
1.7121 0 Td
(miR-483-5p)Tj
4.989 0 Td
(peaked)Tj
3.0103 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.7972 0 Td
(2A)Tj
0 g
(\).)Tj
1.9162 0 Td
(Conversely,)Tj
4.8359 0 Td
(a)Tj
0.6463 0 Td
(different)Tj
-33.8567 -1.2982 Td
(kinetic)Tj
2.9026 0 Td
(of)Tj
1.0035 0 Td
(expression)Tj
4.405 0 Td
(was)Tj
1.6781 0 Td
(instead)Tj
3.0386 0 Td
(observed)Tj
3.7474 0 Td
(for)Tj
1.372 0 Td
(miR-146a,)Tj
4.3086 0 Td
(miR-155)Tj
3.6623 0 Td
(and)Tj
1.7122 0 Td
(its)Tj
1.1281 0 Td
(star)Tj
1.6611 0 Td
(filament,)Tj
3.7191 0 Td
(miR-)Tj
-34.3386 -1.2983 Td
(155)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 214.0724 151.6535 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 218.0976 148.0251 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(,)Tj
0.4365 0 Td
(displaying)Tj
4.2519 0 Td
(an)Tj
1.1906 0 Td
(increasing)Tj
4.2689 0 Td
(level)Tj
1.9843 0 Td
(over)Tj
1.9502 0 Td
(time)Tj
2.0069 0 Td
(during)Tj
2.8913 0 Td
(Mtb)Tj
1.8992 0 Td
(infection)Tj
3.7417 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.7915 0 Td
(2A)Tj
0 g
(\).)Tj
-0.004 Tc
-27.0252 -1.3039 Td
(Microarray)Tj
4.7507 0 Td
(data)Tj
1.9105 0 Td
(were)Tj
2.126 0 Td
(then)Tj
2.0183 0 Td
(validated)Tj
3.8324 0 Td
(by)Tj
1.1792 0 Td
(quantitative)Tj
4.9776 0 Td
(PCR)Tj
2.0693 0 Td
(analyses)Tj
3.4809 0 Td
(\(q-PCR\))Tj
3.6 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
1.2018 0 Td
(indepen-)Tj
-33.3804 -1.2982 Td
(dent)Tj
2.0181 0 Td
(cohort.)Tj
3.0784 0 Td
(According)Tj
4.439 0 Td
(to)Tj
1.0262 0 Td
(microarray,)Tj
4.8982 0 Td
(miR-155,)Tj
3.9288 0 Td
(miR-155)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 428.7685 125.6314 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 435.0047 122.0031 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
1.7291 0 Td
(miR-146a)Tj
4.1385 0 Td
(were)Tj
2.1203 0 Td
(significantly)Tj
-31.4869 -1.2982 Td
(induced)Tj
3.4639 0 Td
(by)Tj
1.1849 0 Td
(Mtb)Tj
1.9162 0 Td
(during)Tj
2.9253 0 Td
(human)Tj
3.0784 0 Td
(DC)Tj
1.6214 0 Td
(infection)Tj
3.7928 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6576 0 Td
(time)Tj
2.0296 0 Td
(dependent)Tj
4.4559 0 Td
(manner)Tj
3.3676 0 Td
(and,)Tj
1.9559 0 Td
(in)Tj
1.0318 0 Td
(particular,)Tj
-32.5131 -1.3039 Td
(miR-155)Tj
3.702 0 Td
(and)Tj
1.7348 0 Td
(its)Tj
1.1452 0 Td
(star)Tj
1.6838 0 Td
(filament)Tj
3.5432 0 Td
(were)Tj
2.126 0 Td
(among)Tj
2.9934 0 Td
(the)Tj
1.4683 0 Td
(top)Tj
1.5421 0 Td
(up-modulated)Tj
5.9299 0 Td
(miRNAs)Tj
3.7077 0 Td
(in)Tj
1.0375 0 Td
(our)Tj
1.627 0 Td
(data)Tj
1.9106 0 Td
(set)Tj
1.3039 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
-35.4554 -1.2983 Td
(2B)Tj
0 g
(\).)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 144.5669 23.6976 re
W* n
q
144.5102 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 428.0881 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(ATG3)Tj
2.8063 0 Td
(impairme)Tj
4.0394 0 Td
(nt)Tj
1.0417 0 Td
(by)Tj
1.2544 0 Td
(Mtb-induc)Tj
4.3157 0 Td
(ed)Tj
1.3111 0 Td
(miR-155)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
102.0472 34.9228 m
256.1953 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Pathogens)Tj
4.9252 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://)Tj
2.9552 0 Td
(doi.org/10.13)Tj
5.7331 0 Td
(71/journal.p)Tj
5.1236 0 Td
(pat.1006)Tj
3.8198 0 Td
(790)Tj
0 g
2.6362 0 Td
(January)Tj
3.7134 0 Td
(4,)Tj
1.0418 0 Td
(2018)Tj
31.8616 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
endstream
endobj
75 0 obj
<>stream
endstream
endobj
76 0 obj
<>stream
endstream
endobj
77 0 obj
<>stream
endstream
endobj
78 0 obj
<>stream
endstream
endobj
79 0 obj
<>stream
BT
66.402 0 Td
(30)Tj
ET
Q
endstream
endobj
80 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 83 0 R/Contents 84 0 R/TrimBox[0 0 612 792]>>
endobj
82 0 obj
<>stream
x-y?{b nh fMГ A6"xā!xƎa'98
0PW"QdR$G8D[ |eT/~y_TWW[O p_%Ow@ ?| H_s @ 01R rE (uI] 'Q @ r՜E vɋ0@nfD @ 01v%/rɜE v) =Έ @ @4H,,K^6n9 r4$
@ .yH,tKwF@ @ !F2g@ng]"qۧ'Q( @ LL vɋF2g@n]
@nO34@ @ 8
69 r;K[N'>>B! @ @`b,K^69 r;]RgO~ϫW&}P @ @
H,,K^6n9;|7]£xu壒` @ &REn# . F:._V5o4W_xqmyU>A%{ @ @xm$sv%/rN }d|o[\Won!m4z])T"T}5fVMxD_ZR|8)w! @ LN vɋF2g@n]
@ng펢u:K$j1Y\㹪1iK! @ rɜE vɋ-@ngm$$GX9Kk-]8fY+:G]̹ʈF$eNo4bԚZH)E@ @ 9 .yH,tK 7Er[5DZK/N[nx+XsY
nOjk@ @`~m$sv%/rN =iV>xu(yӉVk]|4 @ r;Kd"NWpܖuXjTSQcucel)kMaUoX<)]
~*c,eWk{V8o5wBxo @ pm$sv%/rN0-'+L