| First Author | Resende M | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 9 | Pages | 2451-2458 |
| PubMed ID | 31562208 | Mgi Jnum | J:280944 |
| Mgi Id | MGI:6370325 | Doi | 10.4049/jimmunol.1801594 |
| Citation | Resende M, et al. (2019) TNF-Mediated Compensatory Immunity to Mycobacterium avium in the Absence of Macrophage Activation by IFN-gamma. J Immunol 203(9):2451-2458 |
| abstractText | 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 (MPhis) insensitive to IFN-gamma (MIIG) mice have MPhis, 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 MPhi 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 MPhi 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 MPhis, TNF-alpha has a protective role against M. avium. |
