Macrophage Priming Against Glyco-Antigens in the Host Microbiome 2260858

Abstract

Abstract Introduction The mammalian immune system recognizes and responds to a broad variety of glycan antigens, most notoriously including lipopolysaccharides (LPS). LPS lacking O-antigens, known as lipooligosaccharides (LOS) , can also cause strong immune responses, including Guillain-Barré syndrome (GBS), the leading cause of autoimmune flaccid paralysis in the USA. This condition can develop following resolution of food-borne illness and is commonly associated with infection by Campylobacter jejuni, which produces LOS structures that mimic neuronal gangliosides. Methods Previously, we showed that macrophage-like THP-1-derived monocytes can be tolerized against the GM1 ganglioside antigen. Pre-incubation with GM1-mimicking C. jejuni (or purified LOS) results in dampened pro-inflammatory cytokine responses following challenge with GM1-mimicking C. jejuni. Here, we continue utilizing this model, complemented with transcriptomics, to probe macrophage responses to C. jejuni challenge following pre-incubation with opportunistic Enterococcus species originating from guts of multiple animals. Results We show that cholera toxin B subunit (GM1 ganglioside probe) cross-reacts to glyco-antigens produced by opportunistic Enterococcus species found within the gut microbiome. Further, a subset of these species can prime THP-1 cells towards a pro-inflammatory cytokine response upon subsequent exposure to C. jejuni. Conclusion Together, these data further our understanding of how the host immune system recognizes and responds to microbial glycans within the gut microbiome and how this can impact subsequent autoimmune development. These data suggest that colonization with certain Enterococcus species may serve as a potential risk factor for GBS development. Funding Source NIAID R21AI175925, DoD CDMRP PR181475 Topic Categories Mucosal and Regional Immunology (MUC)