title: Effect of exogenous MCP-1 on TLR-2 neutralized murine macrophages and possible mechanisms of CCR-2/TLR-2 and MCP-1 signalling during Staphylococcus aureus infection.
abstract: It has been reported that Staphylococcus aureus survives within macrophages by hijacking host cell surface Toll-like receptor-2 (TLR-2). Moreover, S. aureus infection induced activation of TLR-2 has been reported to downregulate the expression of CC-chemokine receptor-2 (CCR-2), a receptor essential for binding of chemokines to propagate phagocytosis. Thus, we hypothesized that prior blocking of TLR-2 may help normal expression of CCR-2 on cell surface; thereby, administration of exogenous MCP-1 (a CCR-2 ligand) to bind to its free receptors might result in activation of downstream inflammatory signalling cascade. In order to address this, we compared the ability of S. aureus to modulate CCR-2 expression in TLR-2 free or neutralized macrophages in presence or absence of exogenous MCP-1 and associated downstream signalling. Exogenous MCP-1 by interacting CCR-2 leads to the release of nitric oxide and ROS that are important for bacterial clearance. In this experimental setup, the possible molecular pathway connecting an increase in proinflammatory cytokine levels with increased ROS/NO production, and therefore increased killing activity, possibly by involving either MyD88 dependent or RhoA GTPases dependent NF-κB activation or endogenous synthesis of MCP-1, independent of TLR-2-MyD88 pathway. Thus, induction of CCR-2/MCP-1 signalling by macrophages depending on the availability of MCP-1 during S. aureus infection may be important for regulation of septic shock by induction of reactive oxygen species and various cytokines.
authors.affiliation: Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta 700009, West Bengal, India. Electronic address: biswadevbishayi4@gmail.com.
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
authors.affiliation: Department of Physiology, Oxidative Stress and Free Radical Biology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta 700009, West Bengal, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta 700009, West Bengal, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Majhi
authors.affiliation: Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta 700009, West Bengal, India.
authors.forename: Rana
authors.initials: R
authors.lastname: Adhikary
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010587:Phagocytosis / Q000276:immunology; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D020741:rho GTP-Binding Proteins / Q000276:immunology; D020742:rhoA GTP-Binding Protein
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D054390:Receptors, CCR2; D011994:Recombinant Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: CCR-2; Inflammation; Intracellular killing; MCP-1; S. aureus; TLR-2