title: Photo-enhancement of macrophage phagocytic activity via Rac1-mediated signaling pathway: Implications for bacterial infection.
abstract: Phagocytosis and the subsequent destruction of invading pathogens by macrophages are indispensable steps in host immune responses to microbial infections. Low-power laser irradiation (LPLI) has been found to exert photobiological effects on immune responses, but the signaling mechanisms underlying this photobiomodulation of phagocytosis remains largely unknown. Here, we demonstrated for the first time that LPLI enhanced the phagocytic activity of macrophages by stimulating the activation of Rac1. The overexpression of constitutively activated Rac1 clearly enhanced LPLI-induced phagocytosis, whereas the overexpression of dominant negative Rac1 exerted the opposite effect. The phosphorylation of cofilin was involved in the effects of LPLI on phagocytosis, which was regulated by the membrane translocation and activation of Rac1. Furthermore, the photoactivation of Rac1 was dependent on the Src/PI3K/Vav1 pathway. The inhibition of the Src/PI3K pathway significantly suppressed LPLI-induced actin polymerization and phagocytosis enhancement. Additionally, LPLI-treated mice exhibited increased survival and a decreased organ bacterial load when challenged with Listeria monocytogenes, indicating that LPLI enhanced macrophage phagocytosis in vivo. These findings highlight the important roles of the Src/PI3K/Vav1/Rac1/cofilin pathway in regulating macrophage phagocytosis and provide a potential strategy for treating phagocytic deficiency via LPLI.
authors.affiliation: MOE Key Libratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Lu
authors.affiliation: MOE Key Libratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: MOE Key Libratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: xingda@scnu.edu.cn.
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D008089:Listeria monocytogenes / Q000502:physiology*; D028022:Low-Level Light Therapy; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000378:metabolism*; D010587:Phagocytosis / Q000528:radiation effects*; D055503:Protein Multimerization / Q000528:radiation effects; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Anti-infection; Cytoskeletal dynamics; Low-power laser irradiation (LPLI); Macrophage phagocytosis; Rho GTPase