Activin A impairs ActRIIA+ neutrophil recruitment into infected skin of mice
Yan Qi,
Lingling Jiang,
Chengdong Wu,
Jing Li,
Heyuan Wang,
Shiji Wang,
Xintong Chen,
Xueling Cui,
Zhonghui Liu
Affiliations
Yan Qi
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Lingling Jiang
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; Department of Oral Comprehensive Therapy, School and Hospital of Stomatology, Jilin University, Changchun 130021, China
Chengdong Wu
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Jing Li
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Heyuan Wang
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Shiji Wang
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun 130021, China
Xintong Chen
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
Xueling Cui
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; Corresponding author
Zhonghui Liu
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; Corresponding author
Summary: Activin A levels are elevated during multiple severe infections and associated with an increased risk of death. However, the role of activin A in bacterial infection is still unclear. Here, we found that activin A levels were increased during S. aureus skin infection in mice. Administration of activin A increased the bacterial burden and promoted the spread of bacteria in vivo. Moreover, activin A inhibited neutrophil chemotaxis to N-formylmethionine-leucyl-phenylalanine via the type IIA activin receptor (ActRIIA) in vitro and impaired ActRIIA+ neutrophil recruitment to infection foci in vivo. Additionally, we identified a novel subpopulation of neutrophils, ActRIIA+ neutrophils, which exhibit superior phagocytic capacity compared to ActRIIA− neutrophils and possess an N2-like immunoregulatory activity via secreting IL-10 and TGF-β. Taken together, these findings indicate that activin A inhibits the recruitment of ActRIIA+ neutrophils to infected foci, leading to the impairment of bacterial clearance, and thus may hamper early infection control.
