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

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Science Immunology  11 May 2018:
Vol. 3, Issue 23, eaar4135
DOI: 10.1126/sciimmunol.aar4135

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Mycobacteria and metabolism

Since the discovery of Mycobacterium tuberculosis (Mtb) over a century ago, great progress has been made in defining mechanisms of host resistance to tuberculosis (TB). By contrast, our understanding of how 90 to 95% of infected individuals live with chronic TB is extremely limited. Here, Tzelepis et al. examine the role of mitochondrial matrix protein cyclophilin D (CypD) in T cells using a mouse model of Mtb infection. CypD-deficient mice were more susceptible to Mtb infection in spite of enhanced Mtb-specific T cell responses, which has no impact on curbing bacterial loads but substantially increased lung immunopathology. Their findings indicate that CypD is a critical checkpoint of T cell metabolism for regulating disease tolerance in TB.