Polysaccharide capsules equip the human symbiont bacteroides thetaiotaomicron to modulate immune responses to a dominant antigen in the intestine

Samantha Hsieh, Nathan T. Porter, David L. Donermeyer, Stephen Horvath, Gregory Strout, Brian T. Saunders, Nan Zhang, Bernd Zinselmeyer, Eric C. Martens, Thaddeus S. Stappenbeck, Paul M. Allen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Bacteria express multiple diverse capsular polysaccharides (CPSs) for protection against environmental and host factors, including the host immune system. Using a mouse TCR transgenic CD4+ T cell, BuOM, that is specific for B. thetaiotaomicron and a complete set of single CPS-expressing B. thetaiotaomicron strains, we ask whether CPSs can modify the immune responses to specific bacterial Ags. Acapsular B. thetaiotaomicron, which lacks all B. thetaiotaomicron CPSs, stimulated BuOM T cells more strongly than wild-type B. thetaiotaomicron. Despite similar levels of BuOM Ag expression, many single CPS-expressing B. thetaiotaomicron strains were antistimulatory and weakly activated BuOM T cells, but a few strains were prostimulatory and strongly activated BuOM T cells just as well or better than an acapsular strain. B. thetaiotaomicron strains that expressed an antistimulatory CPS blocked Ag delivery to the immune system, which could be rescued by Fc receptor-dependent Ab opsonization. All single CPS- expressing B. thetaiotaomicron strains stimulated the innate immune system to skew toward M1 macrophages and release inflammatory cytokines in an MyD88-dependent manner, with antistimulatory CPS activating the innate immune system in a weaker manner than prostimulatory CPS. The expression of antistimulatory versus prostimulatory CPSs on outer membrane vesicles also regulated immune responses. Moreover, antistimulatory and prostimulatory single CPS-expressing B. thetaiotaomicron strains regulated the activation of Ag-specific and polyclonal T cells as well as clearance of dominant Ag in vivo. These studies establish that the immune responses to specific bacterial Ags can be modulated by a diverse set of CPSs.

Original languageEnglish
Pages (from-to)1035-1046
Number of pages12
JournalJournal of Immunology
Volume204
Issue number4
DOIs
StatePublished - Feb 15 2020

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