Differential Roles of the Calcium Ion Channel TRPV4 in Host Responses to Mycobacterium tuberculosis Early and Late in Infection
| Autor: | Matthias Hauptmann, Ulrich E. Schaible, Wolfgang Liedtke, Vivien Sparr, Wolfgang M. Kuebler, Norbert Reiling, Sumanta Kumar Naik, Kaliprasad Pattanaik, Jacqueline Eich, Barbara Kalsdorf, Avinash Sonawane |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
TRPV4 Multidisciplinary Tuberculosis biology Calcium channel Immunology Virulence 02 engineering and technology 021001 nanoscience & nanotechnology biology.organism_classification medicine.disease Article Proinflammatory cytokine Microbiology Mycobacterium tuberculosis 03 medical and health sciences Transient receptor potential channel Chronic infection 030104 developmental biology medicine lcsh:Q 0210 nano-technology lcsh:Science Molecular Biology |
| Zdroj: | iScience iScience, Vol 23, Iss 6, Pp 101206-(2020) |
| ISSN: | 2589-0042 |
| Popis: | Summary Mycobacterium tuberculosis subverts 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 virulent M. tuberculosis infection 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 controlling M. tuberculosis infection 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 Abstract Highlights • 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 center Molecular Biology; Immunology |
| Databáze: | OpenAIRE |
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