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

doi:10.1016/j.isci.2021.102080

Activin A impairs ActRIIA⁺ neutrophil recruitment into infected skin of mice

iScience. 2021 Jan 21;24(2):102080. doi: 10.1016/j.isci.2021.102080. eCollection 2021 Feb 19.

Authors

Yan Qi¹, Lingling Jiang^{1

2}, Chengdong Wu¹, Jing Li¹, Heyuan Wang¹, Shiji Wang^{1

3}, Xintong Chen⁴, Xueling Cui⁴, Zhonghui Liu¹

Affiliations

¹ Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
² Department of Oral Comprehensive Therapy, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.
³ Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun 130021, China.
⁴ Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Abstract

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.

Keywords: biological sciences; immunology; microbiology.