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MYCOBACTERIUM INFECTION

An unwelcome boost

Elife 9, e52668 (2020)

Attempts to enhance immune responses to Mycobacterium tuberculosis (Mtb) infection can, paradoxically, worsen infection and lead to active tuberculosis. In eLife, Elkington and colleagues investigate the mechanism of disease enhancement by using an in vitro microsphere model of Mtb infection. Both granulomas from patients and microsphere models show expression of the checkpoint pathway molecules PD-1, PD-L1 and PD-L2, and their expression is enhanced by hypoxia. Checkpoint blockade increases proinflammatory cytokine expression in the microspheres, with TNF in particular seeming to enhance Mtb growth. These findings suggest that, while certain inflammatory cytokines are necessary to combat Mtb effectively, their overproduction, such as that elicited by checkpoint blockade, may result in unintended and harmful consequences.

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Correspondence to Zoltan Fehervari.

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Fehervari, Z. An unwelcome boost. Nat Immunol 21, 358 (2020). https://doi.org/10.1038/s41590-020-0659-8

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