Differential roles of the calcium ion channel TRPV4 in host responses to Mycobacterium tuberculosis early and late in infection
Mycobacterium tuberculosis subverts host innate immunity to survive and proliferate within host tissues as prerequisite for progression to active tuberculosis (TB). Non-selective transient receptor potential (TRP) ion channels are involved in host response regulation and are altered upon bacterial infections. Altered expression and localization of TRPV4 in macrophages upon virulent M. tuberculosis infection together with differential distribution of TRPV4 in macrophages in the periphery vs. the center of human TB granulomas indicate a role of TRPV4 in TB.Compared to wild type mice, their Trpv4 deficient littermates showed transiently higher pulmonary M. tuberculosis burden associated with reduced proinflammatory responses. In the absence of TRPV4, activation failed to render macrophages capable to control mycobacterial growth. In contrast, Trpv4 deficient mice were superior to wild type ones in controlling M. tuberculosis infectionin the chronic phase of infection. Here, we demonstrate the importance of Trpv4in host responses to M. tuberculosis, though with opposite functions in the early vs. late phase of infection. Association between Trpv4deficiency and ameliorated chronic infection together with its expression in human tuberculosis lesions indicate the potential of TRPV4as target for host directed therapy.