AUTHOR=Jati Suborno , Sengupta Soham , Sen Malini 

TITLE=Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.628191

DOI=10.3389/fimmu.2020.628191

ISSN=1664-3224

ABSTRACT=<p>Wnt5A signaling facilitates the killing of several bacterial pathogens, but not the non-pathogen <italic>E. coli</italic> DH5α. The basis of such pathogen vs. non-pathogen distinction is unclear. Accordingly, we analyzed the influence of Wnt5A signaling on pathogenic <italic>E. coli</italic> K1 in relation to non-pathogenic <italic>E. coli</italic> K12-MG1655 and <italic>E. coli</italic> DH5α eliminating interspecies variability from our study. Whereas cell internalized <italic>E. coli</italic> K1 disrupted cytoskeletal actin organization and multiplied during Wnt5A depletion, rWnt5A mediated activation revived cytoskeletal actin assembly facilitating K1 eradication. Cell internalized <italic>E. coli</italic> K12-MG1655 and <italic>E. coli</italic> DH5α, which did not perturb actin assembly appreciably, remained unaffected by rWnt5A treatment. Phagosomes prepared separately from Wnt5A conditioned medium treated K1 and K12-MG1655 infected macrophages revealed differences in the relative levels of actin and actin network promoting proteins, upholding that the Wnt5A-Actin axis operates differently for internalized pathogen and non-pathogen. Interestingly, exposure of rWnt5A treated K1 and K12-MG1655/DH5α infected macrophages to actin assembly inhibitors reversed the scenario, blocking killing of K1, yet promoting killing of both K12-MG1655 and DH5α. Taken together, our study illustrates that the state of activation of the Wnt5A/Actin axis in the context of the incumbent bacteria is crucial for directing host response to infection.</p>