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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

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

Revista

Título: Journal of Immunology

Vol. 203

Páginas: 2451-2458

ISSN: 0022-1767

Editora: American Association of Immunologists

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 1 Citação

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8