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Publication : Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis.

First Author  Tzelepis F Year  2018
Journal  Sci Immunol Volume  3
Issue  23 PubMed ID  29752301
Mgi Jnum  J:270517 Mgi Id  MGI:6278587
Doi  10.1126/sciimmunol.aar4135 Citation  Tzelepis F, et al. (2018) Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci Immunol 3(23)
abstractText  Mycobacterium tuberculosis (Mtb) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world's population is chronically infected with Mtb, only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells. Although loss of CypD function in T cells led to enhanced Mtb antigen-specific T cell responses, this increased T cell response had no impact on bacterial burden. Rather, mice containing CypD-deficient T cells exhibited substantially compromised disease tolerance and succumbed to Mtb infection. This study establishes a mechanistic link between T cell-mediated immunity and disease tolerance during Mtb infection.
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