@article{58f710de9c784bcb87bea12506effb8b,
title = "Host phospholipase C-γ1 impairs phagocytosis and killing of mycobacteria by J774A.1 murine macrophages",
abstract = "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.",
keywords = "cytokines, intracellular survival, macrophage response, Mycobacterium tuberculosis, phospholipase C-γ1",
author = "Ruchi Paroha and Rashmi Chourasia and Rupal Rai and Awanish Kumar and Vyas, {Ashish K.} and Chaurasiya, {Shivendra K.} and Singh, {Anirudh K.}",
note = "Funding Information: This study was supported by research grant from the Department of Biotechnology, Mininstry of Science and Technology, India (Grant # BT/PR8640/AGR/36/785/2013) to SKC. The SKC laboratory also had support from Science and Engineering Research Board, Department of Science and Technology, India (Grant # SB/Y/LS-143/2013) and University Grants Commission, India (Grant # 30-12/2014(BSR)). The authors also acknowledge the financial support by Maulana Azad National Institute of Technology, Bhopal sanctioned to SKC. RP is the recipient of DST-INSPIRE Senior Research Fellowship from the Department of Science and Technology, India. AKS is the recipient of Ramalingaswami Re-Entry Fellowship from the Department of Biotechnology, India. AKV is the recipient of DST-INSPIRE Faculty Fellowship, from the Department of Science and Technology, India. We are grateful to Prof. Kishore K Srivastava, CSIR-Central Drug Research Institute, Lucknow, for providing mycobacterial cultures and J774A.1 cell lines. The funders had no role in the design and execution of the study. Funding Information: This study was supported by research grant from the Department of Biotechnology, Mininstry of Science and Technology, India (Grant # BT/PR8640/AGR/36/785/2013) to SKC. The SKC laboratory also had support from Science and Engineering Research Board, Department of Science and Technology, India (Grant # SB/Y/LS‐143/2013) and University Grants Commission, India (Grant # 30‐12/2014(BSR)). The authors also acknowledge the financial support by Maulana Azad National Institute of Technology, Bhopal sanctioned to SKC. RP is the recipient of DST‐INSPIRE Senior Research Fellowship from the Department of Science and Technology, India. AKS is the recipient of Ramalingaswami Re‐Entry Fellowship from the Department of Biotechnology, India. AKV is the recipient of DST‐INSPIRE Faculty Fellowship, from the Department of Science and Technology, India. We are grateful to Prof. Kishore K Srivastava, CSIR‐Central Drug Research Institute, Lucknow, for providing mycobacterial cultures and J774A.1 cell lines. The funders had no role in the design and execution of the study. Publisher Copyright: {\textcopyright} 2020 The Societies and John Wiley & Sons Australia, Ltd",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/1348-0421.12839",
language = "English (US)",
volume = "64",
pages = "694--702",
journal = "Microbiology and Immunology",
issn = "0385-5600",
publisher = "Center for Academic Publications Japan",
number = "10",
}