TY - JOUR
T1 - Phospholipase C-γ2 promotes intracellular survival of mycobacteria
AU - Paroha, Ruchi
AU - Chaurasiya, Shivendra K.
AU - Chourasia, Rashmi
N1 - Funding Information:
Department of Biotechnology, Ministry of Science and Technology, Grant/Award Number: BT/PR8640/AGR/36/785/2013; Science and Engineering Research Board, Grant/Award Number: SB/Y/LS‐143/ 2013; University Grants Commission, Grant/Award Number: 0‐12/2014(BSR)
Funding Information:
This study was funded by Department of Biotechnology, India (Grant #BT/PR8640/AGR/36/785/2013). Our lab has also been supported by 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). All these grants were sanctioned to Dr Shivendra K Chaurasiya. We are grateful to Prof Kishore K Srivastava, CSIR-Central Drug Research Institute, Lucknow, for providing mycobacterial cultures and J774A.1 cell lines. Authors also thank Dr Rajaneesh Anupam, Dept. of Biotechnology, Dr. Hari Singh Gour University, Sagar for constructive review of the manuscript. RP is the recipient of DST-INSPIRE Junior Research Fellowship. Real time PCR facility at SIC, Dr HS Gour University, Sagar was used on payment basis.
Funding Information:
This study was funded by Department of Biotechnology, India (Grant #BT/PR8640/AGR/36/785/2013). Our lab has also been supported by 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). All these grants were sanctioned to Dr Shivendra K Chaurasiya. We are grateful to Prof Kishore K Srivastava, CSIR‐Central Drug Research Institute, Lucknow, for providing mycobacterial cultures and J774A.1 cell lines. Authors also thank Dr Rajaneesh Anupam, Dept. of Biotechnology, Dr. Hari Singh Gour University, Sagar for constructive review of the manuscript. RP is the recipient of DST‐INSPIRE Junior Research Fellowship. Real time PCR facility at SIC, Dr HS Gour University, Sagar was used on payment basis.
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/4
Y1 - 2019/4
N2 - Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not Mycobacterium smegmatis (MS) induces phosphorylation of PLC-γ2 at tyrosine 1217 in J774A.1 cells. Small interfering RNA–mediated knockdown of PLC-γ2 expression leads to the enhanced killing of both MS and Mtb by these cells suggesting that Mtb activates PLC-γ2 to promote its intracellular survival within macrophages. Knockdown of PLC-γ2 also lead to increased uptake of Mtb but not MS by J774.A.1 cells. Further, we have observed that PLC-γ2 was required for Mtb-induced inhibition of expression of proinflammatory cytokine tumor necrosis factor-α, inducible nitric oxide synthase, and chemokine (C-C motif) ligand 5 (RANTES). Altogether, our results for the first time demonstrate that Mtb induces activation of macrophages PLC-γ2 to inhibit their mycobactericidal response.
AB - Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not Mycobacterium smegmatis (MS) induces phosphorylation of PLC-γ2 at tyrosine 1217 in J774A.1 cells. Small interfering RNA–mediated knockdown of PLC-γ2 expression leads to the enhanced killing of both MS and Mtb by these cells suggesting that Mtb activates PLC-γ2 to promote its intracellular survival within macrophages. Knockdown of PLC-γ2 also lead to increased uptake of Mtb but not MS by J774.A.1 cells. Further, we have observed that PLC-γ2 was required for Mtb-induced inhibition of expression of proinflammatory cytokine tumor necrosis factor-α, inducible nitric oxide synthase, and chemokine (C-C motif) ligand 5 (RANTES). Altogether, our results for the first time demonstrate that Mtb induces activation of macrophages PLC-γ2 to inhibit their mycobactericidal response.
KW - inducible nitric oxide synthase
KW - intracellular survival
KW - Mycobacterium smegmatis
KW - Mycobacterium tuberculosis
KW - phospholipase C-γ2
KW - tumor necrosis facto-α
KW - tyrosine phosphorylation
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U2 - 10.1002/jcb.27783
DO - 10.1002/jcb.27783
M3 - Article
C2 - 30317660
AN - SCOPUS:85054916560
SN - 0730-2312
VL - 120
SP - 5062
EP - 5071
JO - Journal of supramolecular structure and cellular biochemistry
JF - Journal of supramolecular structure and cellular biochemistry
IS - 4
ER -