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Host phospholipase C‐γ1 impairs phagocytosis and killing of mycobacteria by J774A.1 murine macrophages
Author(s) -
Paroha Ruchi,
Chourasia Rashmi,
Rai Rupal,
Kumar Awanish,
Vyas Ashish K.,
Chaurasiya Shivendra K.,
Singh Anirudh K.
Publication year - 2020
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12839
Subject(s) - biology , microbiology and biotechnology , chemokine , mycobacterium tuberculosis , intracellular , phagocytosis , intracellular parasite , pathogen , macrophage , gene knockdown , internalization , phospholipase c , tumor necrosis factor alpha , cell culture , tuberculosis , immunology , immune system , signal transduction , receptor , in vitro , biochemistry , genetics , medicine , pathology
Macrophages represent the first line of defense against invading Mycobacterium tuberculosis (Mtb). In order to enhance intracellular survival, Mtb targets various components of the host signaling pathways to limit macrophage functions. The outcome of Mtb infection depends on various factors derived from both host and pathogen. A detailed understanding of such factors operating during interaction of the pathogen with the host is a prerequisite for designing new approaches for combating mycobacterial infections. This work analyzed the role of host phospholipase C‐γ1 (PLC‐γ1) in regulating mycobacterial uptake and killing by J774A.1 murine macrophages. Small interfering RNA mediated knockdown of PLC‐γ1 increased internalization and reduced the intracellular survival of both Mtb and Mycobacterium smegmatis (MS) by macrophages. Down‐regulation of the host PLC‐γ1 was observed during the course of mycobacterial infection within these macrophages. Finally, Mtb infection also suppressed the expression of pro‐inflammatory cytokine tumor necrosis factor‐α and chemokine (C‐C motif) ligand 5 (RANTES) which was restored by knocking down PLC‐γ1 in J774A.1 cells. These observations suggest a role of host PLC‐γ1 in the uptake and killing of mycobacteria by murine macrophages.