Polysaccharide Capsules Equip the Human Symbiont Bacteroides thetaiotaomicron to Modulate Immune Responses to a Dominant Antigen in the Intestine
Artikel i vetenskaplig tidskrift, 2020

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, BθOM, 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 BθOM T cells more strongly than wild-type B. thetaiotaomicron Despite similar levels of BθOM Ag expression, many single CPS-expressing B. thetaiotaomicron strains were antistimulatory and weakly activated BθOM T cells, but a few strains were prostimulatory and strongly activated BθOM 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.

Författare

Samantha Hsieh

Washington University in St. Louis

Nathan Porter

Chalmers, Biologi och bioteknik, Industriell bioteknik

David L. Donermeyer

Washington University in St. Louis

Stephen Horvath

Washington University in St. Louis

Gregory Strout

Washington University in St. Louis

Brian T. Saunders

Washington University in St. Louis

Nan Zhang

Washington University in St. Louis

Bernd Zinselmeyer

Washington University in St. Louis

Eric C. Martens

University of Michigan Medical School

Thaddeus S. Stappenbeck

Washington University in St. Louis

Paul M. Allen

Washington University in St. Louis

Journal of Immunology

0022-1767 (ISSN) 1550-6606 (eISSN)

Vol. 204 4 1035-1046

Ämneskategorier

Immunologi

Cell- och molekylärbiologi

Immunologi inom det medicinska området

DOI

10.4049/jimmunol.1901206

PubMed

31900343

Mer information

Senast uppdaterat

2020-04-03