TNF-Mediated Compensatory Immunity to Mycobacterium avium in the Absence of Macrophage Activation by IFN-gamma

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Resende, M (Author) Other; Cardoso, MS (Author) Other; Frois Martins, R (Author) Other; Margarida Borges (Author) FFUP; Jordan, MB (Author) Other; Castro, AG (Author) Other; Appelberg, R (Author) Other

Journal

Title: Journal of Immunology

Vol. 203

Pages: 2451-2458

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00R-62R

DOI: 10.4049/jimmunol.1801594

Abstract (EN): Granuloma formation is a hallmark of several infectious diseases, including those caused by Mycobacterium sp. These structures are composed of accumulations of inflammatory cells, and it has been shown that cytokines such as IFN-gamma and TNF-alpha are required for granuloma assembly during M. avium infections in mice. Macrophages (M Phi s) insensitive to IFN-gamma (MIIG) mice have M Phi s, monocytes, and dendritic cells that are unresponsive to IFN-gamma. We observed that although IFN-gamma(-/-)mice present an exacerbated infection, the same is not true for MIIG animals, where the same levels of protection as the wild-type animals were observed in the liver and partial protection in the spleen. Unlike IFN-gamma(-/-) mice, MIIG mice still develop well-defined granulomas, suggesting that IFN-gamma-mediated M Phi activation is not required for granuloma assembly. This work also shows that MIIG animals exhibit increased cell recruitment with higher CD4(+) T cells numbers as well as increased IFN-gamma and TNF-alpha expression, suggesting that TNF-alpha may have a role in protection and may compensate the lack of M Phi response to IFN-gamma in the MIIG model. TNF-alpha-deficient MIIG mice (MIIG.TNF-alpha(-/-)) exhibited increased bacterial burdens when compared with MIIG mice. These results suggest that in the absence of IFN-gamma signaling in M Phi s, TNF-alpha has a protective role against M. avium.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8