TLR2 agonist Pam3CSK4 enhances the antibacterial functions of GM-CSF induced neutrophils to methicillin-resistant Staphylococcus aureus

Publication date: Available online 15 March 2019Source: Microbial PathogenesisAuthor(s): Yiguo Chen, Shanshan Lu, Yong Zhang, Jinmei Yu, Linqiang Deng, Hui Chen, Yujuan Zhang, Nanjin Zhou, Keng Yuan, Lizhi Yu, Zhanghua Xiong, Xiaomei Gui, Yanrong Yu, Weiping MinAbstractA proliferation of studies have demonstrated that the toll-like receptor 2 (TLR2) pathway affects the chemotaxis, phagocytosis, and cytokine release of neutrophils when pathogens invade. Our previous studies have demonstrated that pretreatment with high doses of Pam3CSK4 (>25 μg/ml) improves the antimicrobial activity of neutrophils, however, short-lived neutrophils limit their therapeutic functions. Here, we used granulocyte macrophage-colony stimulating factor (GM-CSF) to generate neutrophils from murine bone marrow, and assessed their effect on the immune response against methicillin-resistant Staphylococcus aureus. As comparing with classical method of generating neutrophils directly from murine bone marrow, our findings show that pretreatment with Pam3CSK4 enhanced the phagocytic and killing activities against MRSA by the GM-CSF induced neutrophils (GM-CSF neutrophils). Chemotaxis of GM-CSF induced neutrophils was significantly increased after the pretreatment with Pam3CSK4. Furthermore, Pam3CSK4 pretreatment enhanced iNOS, CRAMP, TNF-α, IL-1β, IL-10, and IL-6 expression. Finally, we observed that p38MAPK and Akt phosphorylation kinases were increased significantly in GM-CSF neutrophils pretreatment w...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research