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

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 inmice. 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-beta. 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.