Photo-enhancement of macrophage phagocytic activity via Rac1-mediated signaling pathway: Implications for bacterial infection |
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| Institution: | 3. Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China;4. Child Health Institute of New Jersey and Department of Pharmacology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08901;5. Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854;1. Bosch Institute, University of Sydney, NSW 2006, Australia;2. Discipline of Physiology, University of Sydney, NSW 2006, Australia;3. Save Sight Institute & Clinical Ophthalmology, University of Sydney & Sydney Eye Hospital, NSW 2000, Australia;4. Dementia Research Unit, School of Medical Sciences, University of New South Wales, NSW 2052, Australia;5. Neuroscience Research Australia, Sydney, NSW 2031, Australia;6. Discipline of Anatomy & Histology, University of Sydney, NSW 2006, Australia;1. Vielight Inc., Toronto, ON, Canada;2. Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada;3. Saltmarche Health & Associates Inc., Orangeville, ON, Canada;4. Departments of Radiology & Biomedical Imaging and Psychiatry, University of California, San Francisco, CA, United States;1. Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou, Henan, China;2. Department of Pharmacy, People’s Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China;3. Department of Pharmacy, People’s Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China;4. School of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan University of Science and Technology, Luoyang, Henan, China;5. Department of Clinical Pharmacy, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China |
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| 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. |
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| Keywords: | Low-power laser irradiation (LPLI) Macrophage phagocytosis Cytoskeletal dynamics Rho GTPase Anti-infection |
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