Properties and Mechanisms of the Innate and Adaptive Mucus Barrier Against Pathogens

Viruses and intracellular obligate bacteria must penetrate across mucus to establish infections; thus, mucus represents the body’s first line of defense.  Nevertheless, the precise molecular and biophysical mechanisms by which mucus can block the translocation of pathogens in mucus remains not well understood.  I will present our recent discovery that antibodies possess a glycan-dependent “muco-trapping” effector function that provides an exceptionally potent yet largely unrecognized mechanism of immune protection at mucosal surfaces of the female reproductive, gastrointestinal and respiratory tracts.  Specifically, mucosal antibodies can help immobilize both viral and motile bacterial pathogens through interactions between N-glycans on Fc domain and mucins at sub-neuralizing antibody levels, and trapping viruses in mucus alone is sufficient to block viral transmission in vivo.  I will present unpublished findings on the precise influence of sugar patterns on IgG-Fc, as well as antibody-mucin interactions across the menstrual cycle and in the presence of different commensal microbial communities.   I will also present unpublished work on how specific strains of commensal Lactobacilli can critically compromise the innate barrier properties of mucins against HIV and other enveloped viruses.  Together, these results contribute to an emerging understanding of the complex interplay between the host immune system, pathogen and commensals.