Pro-Inflammatory Response of Human Monocyte-Derived Dendritic Cells to Bacterial Biofilms 2310119

Abstract Introduction Many human bacterial pathogens, including Uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs), can form biofilms. Bacterial biofilms are multicellular communities reinforced by amyloids that protect the bacteria from environmental stress, including antibiotics, promoting chronic infections. The recognition of biofilms by innate immune cells remains under-investigated. Our labs have previously shown that curli, the amyloid expressed by Enterobacteriaceae like UPEC during biofilm formation, activate murine dendritic cells. Many PAMPs in biofilms can mediate innate immune activation, and it is pivotal to understand their roles in host defense. Methods We investigated the response of human monocyte-derived dendritic cells (hu-moDCs) from healthy donors to UPEC biofilms. To compare the role of two well-known PAMPs in biofilms, LPS and curli, we utilized UPEC lab strain UTI-89 wild type (WT) and its msbB mutant, which produces a pentacylated LPS that is not immunostimulatory for hu-moDCs. Using bulk RNASeq, Flow Cytometry and proteomics, we compared hu-moDC responses to these biofilms and to individual biofilm components LPS and curli. Results We found that exposure to biofilms strongly activated hu-moDCs, inducing upregulation of surface expression of MHC and costimulatory molecules and secretion of pro-inflammatory cytokines and chemokines in a dose-dependent manner, showing similar activation with WT and msbB mutant biofilms, therefore irrespective of the presence of LPS. Curli and LPS also induced similar responses. Transcriptional analysis showed specific molecular pathways for ongoing investigation. Conclusion Our data suggest that not only can biofilms activate hu-moDCs, but they also do that in an LPS-independent manner, highlighting curli as a major biofilm-associated PAMP. Deeper knowledge of the innate immune response to biofilms is an important step in understanding the full immune response to biofilms. Funding Source N/A Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)