Exponential growth of lung granulomas after Mycobacterium tuberculosis infection

Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains a global health problem of enormous proportions, causing 2 million deaths each year. It is estimated that one-third of the world population has been exposed to or carry the pathogen, with 8 million new cases of active disease per year. Both innate and adaptive immunity responses are known to play a pivotal role in establishing a protective immunity during Mtb infection, and latest studies suggested that additional genetic factors could affect the outcome of infection. The interaction between the pathogen and the host immune system induces granulomas development, structures characterized by bacterial components and immune cells that represent key pathologic features of TB. Moreover, neogenesis of lymphoid tissues in the lungs after Mtb infection contributes to the generation of local antigen-specific responses. To test the role of Interferon Regulatory Factor 8 (IRF8) in host defenses against Mtb, we used mice deficient in IRF8 gene (IRF8-/- mice), and we investigated the mycobacterial load and dissemination in the lesions, the functional and structural properties of infiltrated tissues as well as the distribution and interactions of host immune cells. This study shows that this transcription factor is essential for the induction of an effective adaptive immunity associated to the generation of competent pulmonary newly formed lymphoid structures and granulomas characterized by a proper influx of immune cells able to restrain Mtb infection. Together, these findings support the role of IRF8 as an important regulator of host defenses against TB.