Differential Roles of the Calcium Ion Channel TRPV4 in Host Responses to Mycobacterium tuberculosis Early and Late in Infection
Sumanta Kumar Naik,
Kaliprasad Pattanaik,
Jacqueline Eich,
Vivien Sparr,
Matthias Hauptmann,
Barbara Kalsdorf,
Norbert Reiling,
Wolfgang Liedtke,
Wolfgang M. Kuebler,
Ulrich E. Schaible,
Avinash Sonawane
Affiliations
Sumanta Kumar Naik
School of Biotechnology, KIIT University, Odisha 751024, India; Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Kaliprasad Pattanaik
School of Biotechnology, KIIT University, Odisha 751024, India
Jacqueline Eich
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Vivien Sparr
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Matthias Hauptmann
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Barbara Kalsdorf
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Norbert Reiling
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany
Wolfgang Liedtke
Duke University Center for Translational Neuroscience, Durham, NC 27710, USA
Wolfgang M. Kuebler
Institute of Physiology, Charité–Universitäts-medizin, Berlin, Germany
Ulrich E. Schaible
Program Area Infections, Department of Cellular Microbiology, Research Center Borstel-Leibniz Lung Center, Borstel 23845, Germany; Corresponding author
Avinash Sonawane
School of Biotechnology, KIIT University, Odisha 751024, India; Discipline of Biosciences & Biomedical Engineering, Indian Institute of Technology, Indore, Madhya Pradesh 453552, India; Corresponding author
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.