Following Mycobacterium tuberculosis (Mtb)
infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through
granuloma formation and neogenesis of lymphoid structures (LS).
Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study,
IRF-8 deficient mice (IRF-8⁻/⁻) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of
infection was compared with that induced in wild-type (WT-B6) counterparts.
Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8⁻/⁻ mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8⁻/⁻, uncontrolled growth of pulmonary
granulomas and impaired development of LS were observed, associated with unbalanced homeostatic
chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late
infection stages. Our data define
IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in
granulomas and LS required to restrain Mtb
infection. Moreover, IRF-8⁻/⁻ mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions.