Host Response to Bacterial Pathogens and Non-Pathogens is Determined by Wnt5A Mediated Actin Organization

Abstract

Wnt5A signaling facilitates the killing of numerous bacterial pathogens but not non-pathogens. The basis of such distinction in killing remains unclear. Accordingly, we analyzed the influence of Wnt5A signaling on pathogenic E.coli K1 in relation to non-pathogenic E.coli K12-MG1655 and E.coli DH5α. We found that bacterial killing by macrophages is dictated by the effect of Wnt5A aided actin assembly on the incumbent bacteria. Actin assembly mediated by Wnt5A signaling antagonized the disruptive influence of internalized E.coli K1 on cytoskeletal actin facilitating its eradication. However, internalized E.coli K12-MG1655 and E.coli DH5α, which stabilize the actin cytoskleton remained unaffected by Wnt5A. Interestingly, actin assembly inhibitors altered bacterial phagosome compositions, supporting survival of K1, yet promoting killing of both K12-MG1655 and DH5α, in Wnt5A activated macrophages. Taken together, our study reveals the importance of Wnt5A signaling dependent assembly of cytoskeletal actin in determining the outcome of host response to bacterial pathogens and non-pathogens.