1. TNFRp75-dependent immune regulation of alveolar macrophages and neutrophils during early Mycobacterium tuberculosis and Mycobacterium bovis BCG infection.
- Author
-
Walters A, Keeton R, Labuschagné A, Hsu NJ, and Jacobs M
- Subjects
- Animals, Apoptosis immunology, Cattle, Cells, Cultured, Female, Lung immunology, Male, Mice, Mice, Inbred C57BL, Mycobacterium bovis immunology, Mycobacterium tuberculosis immunology, Receptors, Tumor Necrosis Factor, Type I immunology, Signal Transduction immunology, Tumor Necrosis Factor Decoy Receptors immunology, Virulence immunology, BCG Vaccine immunology, Macrophages, Alveolar immunology, Neutrophils immunology, Receptors, Tumor Necrosis Factor, Type II immunology, Tuberculosis immunology, Tuberculosis, Bovine immunology
- Abstract
TNF signalling through TNFRp55 and TNFRp75, and receptor shedding is important for immune activation and regulation. TNFRp75 deficiency leads to improved control of Mycobacterium tuberculosis (M. tuberculosis) infection, but the effects of early innate immune events in this process are unclear. We investigated the role of TNFRp75 on cell activation and apoptosis of alveolar macrophages and neutrophils during M. tuberculosis and M. bovis BCG infection. We found increased microbicidal activity against M. tuberculosis occurred independently of IFNy and NO generation, and displayed an inverse correlation with alveolar macrophages (AMs) apoptosis. Both M. tuberculosis and M. bovis BCG induced higher expression of MHC-II in TNFRp75
-/- AMs; however, M bovis BCG infection did not alter AM apoptosis in the absence of TNFRp75. Pulmonary concentrations of CCL2, CCL3 and IL-1β were increased in TNFRp75-/- mice during M, bovis BCG infection, but had no effect on neutrophil responses. Thus, TNFRp75-dependent regulation of mycobacterial replication is virulence dependent and occurs independently of early alveolar macrophage apoptosis and neutrophil responses., (© 2020 John Wiley & Sons Ltd.)- Published
- 2021
- Full Text
- View/download PDF