摘要：SummaryMycobacterium tuberculosissubverts host immunity to proliferate within host tissues. Non-selective transient receptor potential (TRP) ion channels are involved in host responses and altered upon bacterial infections. Altered expression and localization of TRPV4 in macrophages upon virulentM. tuberculosisinfection together with differential distribution of TRPV4 in human tuberculosis (TB) granulomas indicate a role of TRPV4 in TB. Compared with wild-type mice, Trpv4-deficient littermates showed transiently higher mycobacterial burden and reduced proinflammatory responses. In the absence of TRPV4, activation failed to render macrophages capable of controlling mycobacteria. Surprisingly, Trpv4-deficient mice were superior to wild-type ones in controllingM. tuberculosisinfection in the chronic phase. Thus, Trpv4 is important in host responses to mycobacteria, although with opposite functions early versus late in infection. Ameliorated chronic infection in the absence of Trpv4 and its expression in human TB lesions indicate TRPV4 as putative target for host-directed therapy.Graphical AbstractDisplay OmittedHighlights•Mtb down-modulates TRPV4 expression in macrophages•Trpv4−/−macrophages cannot be activated to drive phagosome maturation and NO production•Trpv4-deficient mice are more resistant to Mtb•TRPV4-positive macrophages in the periphery of human granuloma but not at the centerMolecular Biology; Immunology
