TY - JOUR
T1 - Polysaccharide capsules equip the human symbiont bacteroides thetaiotaomicron to modulate immune responses to a dominant antigen in the intestine
AU - Hsieh, Samantha
AU - Porter, Nathan T.
AU - Donermeyer, David L.
AU - Horvath, Stephen
AU - Strout, Gregory
AU - Saunders, Brian T.
AU - Zhang, Nan
AU - Zinselmeyer, Bernd
AU - Martens, Eric C.
AU - Stappenbeck, Thaddeus S.
AU - Allen, Paul M.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants F30DK114950 (to S. Hsieh) and R21AI142257 (to P.M.A. and E.C.M.). The Washington University Center for Cellular Imaging is supported by Washington University School of Medicine, The Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (CDI‐CORE‐2015‐505), and the Foundation for Barnes‐Jewish Hospital (3770).
Publisher Copyright:
© 2020 by The American Association of Immunologists, Inc.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079023312&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1901206
DO - 10.4049/jimmunol.1901206
M3 - Article
C2 - 31900343
AN - SCOPUS:85079023312
SN - 0022-1767
VL - 204
SP - 1035
EP - 1046
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -