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Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Authors :
Rocca, S
Schiavoni, G
Sali, Michela
Anfossi, Ag
Abalsamo, L
Palucci, Ivana
Mattei, F
Sanchez, M
Giagu, A
Antuofermo, E
Fadda, Giovanni
Belardelli, F
Delogu, Giovanni
Gabriele, L.
Sali, Michela (ORCID:0000-0003-3609-2990)
Delogu, Giovanni (ORCID:0000-0003-0182-8267)
Rocca, S
Schiavoni, G
Sali, Michela
Anfossi, Ag
Abalsamo, L
Palucci, Ivana
Mattei, F
Sanchez, M
Giagu, A
Antuofermo, E
Fadda, Giovanni
Belardelli, F
Delogu, Giovanni
Gabriele, L.
Sali, Michela (ORCID:0000-0003-3609-2990)
Delogu, Giovanni (ORCID:0000-0003-0182-8267)
Publication Year :
2013

Abstract

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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1105014696
Document Type :
Electronic Resource