Differential Toll like receptor expression in cystic fibrosis patients' airways during rhinovirus infection

Objectives: Since an inappropriate and sustained activation of TLRs may contribute to a chronic inflammatory response resulting in detrimental effects in cystic fibrosis (CF) patients, we sought to examine whether HRV infection might alter the respiratory expression of TLRs according to the microbiological status of CF patients. Methods: Respiratory samples were collected from the respiratory tract of CF patients (n = 294) over a period of 12 months. In addition to the usual microbiological investigation, HRV-RNA detection and typing were performed by RT-PCR and sequencing. HRV viral load and TLRs levels were measured by RT-Real Time PCR. Results: HRV-RNA was detected in 80 out of 515 respiratory samples (15.5%) with a similar rate in all age groups (0–10 years, 11–24 years, ≥ 25 years). Patients infected with different HRV A, B and C species exhibited higher levels of TLR2, TLR4 and TLR8 as compared to HRV negative patients. Moreover, the expression level of TLR2, TLR4 and TLR8 correlated with high level of HRV viral load. HRV positive patients co-colonized by Staphylococcus aureus or Pseudomonas aeruginosa showed also enhanced amounts of TLR2 and TLR2/4-mRNAs expression respectively. In the case of presence of both bacteria, TLR2, TLR4, TLR8 and TLR9 levels are elevated in positive HRV patients. Conclusions: TLRs, especially TLR2 and TLR4, increased in HRV positive CF individuals and varies according to the presence of S. aureus, P. aeruginosa and both bacteria.