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

TNF-Mediated Compensatory Immunity to Mycobacterium avium in the Absence of Macrophage Activation by IFN-γ. J Immunol. 2019 Sep 27;: Authors: Resende M, Cardoso MS, Fróis-Martins R, Borges M, Jordan MB, Castro AG, Appelberg R Abstract 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-γ and TNF-α are required for granuloma assembly during M. avium infections in mice. Macrophages (MΦs) insensitive to IFN-γ (MIIG) mice have MΦs, monocytes, and dendritic cells that are unresponsive to IFN-γ. We observed that although IFN-γ-/- 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-γ-/- mice, MIIG mice still develop well-defined granulomas, suggesting that IFN-γ-mediated MΦ 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-γ and TNF-α expression, suggesting that TNF-α may have a role in protection and may compensate the lack of MΦ response to IFN-γ in the MIIG model. TNF-α-deficient MIIG mice (MIIG.TNF-α-/-) exhibited increased bacterial burdens when compared...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research