Brucella abortus infection modulates mitochondrial dynamics and immunometabolism in macrophages via endoplasmic reticulum stress sensor IRE1α.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B566
Abstract ID: 4299

Presenting Author:
Sergio C Oliveira , Professor at Univ. de São Paulo

Abstract:

In this study, we aimed to evaluate the role of mitochondrial dynamics in the pathogenesis of Brucella abortus infection. Macrophages were treated with 50 mM 4m8c (IRE1α inhibitor), infected with B. abortus and the expression of mitofusin 1 and 2 in mitochondrial fusion and dynamin-related protein 1 (DRP1) and mitochondrial fission 1 protein (FIS1) in fission were determined by qPCR.  We also determined mitochondrial respiration during infection and after IRE1α blockage. Finally, we assessed B. abortus replication in macrophages treated with mitochondrial stress inducers. Our results indicated that infection with B. abortus enhanced DRP1 and FIS1 expression levels that were reduced upon IRE1a inhibition. These results indicate that B. abortus infection alters the fission/fusion balance, inducing mitochondrial fragmentation in an ER stress-dependent manner. We also observed that Brucella impairs mitochondrial respiration during infection. Furthermore, we evaluated cytokine secretion in DRP1 KO infected cells and demonstrated that absence of DRP1 reduced IFN-b expression and CXCL10 secretion. Lastly, B. abortus increases replication in macrophages when the cells were treated with mitochondrial stress inducers. In this study, we demonstrated that mitochondrial dysfunction favored B. abortus intracellular replication, suggesting that the manipulation of mitochondrial dynamics by bacteria could be a major determinant of disease outcome.