title: Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.
abstract: The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Yi-Guo
authors.initials: YG
authors.lastname: Chen
authors.affiliation: Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi 330006, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Lin-Qiang
authors.initials: LQ
authors.lastname: Deng
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi 330006, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Nan-Jin
authors.initials: NJ
authors.lastname: Zhou
authors.affiliation: Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi 330006, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Keng
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Yu
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Zhang-Hua
authors.initials: ZH
authors.lastname: Xiong
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Gui
authors.affiliation: Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi 330006, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Yu
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.
authors.forename: Xiao-Mu
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Medical Laboratory, Jiangxi Provincial People's Hospital, and Institute of Immunotherapy, Nanchang University, Nanchang, Jiangxi 330008 China.|Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi 330006, China.|Jiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, Jiangxi 330006, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017463:Receptors, Complement 3b / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology
chemical_list: D016207:Cytokines; C485701:Fcgr1 protein, mouse; C485700:Fcgr3 protein, mouse; D055666:Lipopeptides; D016177:Macrophage-1 Antigen; C508075:Pam(3)CSK(4) peptide; D017463:Receptors, Complement 3b; D017452:Receptors, IgG; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2