Phospholipase C-γ2 promotes intracellular survival of mycobacteria

Ruchi Paroha, Shivendra K. Chaurasiya, Rashmi Chourasia

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5062-5071
Number of pages10
JournalJournal of Cellular Biochemistry
Volume120
Issue number4
DOIs
StatePublished - Apr 2019
Externally publishedYes

Keywords

  • inducible nitric oxide synthase
  • intracellular survival
  • Mycobacterium smegmatis
  • Mycobacterium tuberculosis
  • phospholipase C-γ2
  • tumor necrosis facto-α
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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