Document details

TNF-mediated compensatory immunity to mycobacterium avium in the absence of macrophage activation by IFN-γ

Author(s): Resende, Mariana ; Cardoso, Marcos S. ; Fróis-Martins, Ricardo ; Borges, Margarida ; Jordan, Michael B. ; Castro, António G. ; Appelberg, Rui

Date: 2019

Persistent ID: http://hdl.handle.net/1822/67360

Origin: RepositóriUM - Universidade do Minho

Subject(s): Animals; CD4-Positive T-Lymphocytes; Granuloma; Interferon-gamma; Macrophage Activation; Mice; Mice, Inbred C57BL; Mycobacterium avium; Signal Transduction; Tumor Necrosis Factor-alpha; Science & Technology; Ciências Médicas::Medicina Básica


Description

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 with MIIG mice. These results suggest that in the absence of IFN-γ signaling in MΦs, TNF-α has a protective role against M. avium.

Structured program on bioengineered therapies for infectious diseases and tissue regeneration (Grant NORTE-01-0145-FEDER-000012) supported by Norte Portugal Regional Operational Programme (NORTE 2020, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund); by Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation, Portugal 2020; by Portuguese funds through the Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (Grant POCI-01-0145-FEDER-007274); by Grant POCI-01-0145-FEDER-028463, Fundos Europeus Estruturais e de Investimento, and FCT (I.P. Grant PTDC/SAU-INF/28463/2017). M.R. was supported by FCT Grant SFRH/BD/89871/2012

Document Type Journal article
Language English
Contributor(s) Universidade do Minho
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