Resumen
Regulatory B (Breg) cells are known to modulate immune responses through predominantly interleukin-10 (IL-10)-dependent mechanisms and can be hypothetically divided into innate and adaptive subsets based on the nature of their activating signals. However, the specific role of different Breg subsets in modulating immune responses remains ambiguous. Here we have shown that Chlamydia induces IL-10-producing splenic B-cell populations consisting of CD43 + and CD43 - subsets of IgM hi IgD lo innate-like B (ILB) cells in vitro. While CD43 + IL-10-producing B cells displayed innate type features and were readily induced by Chlamydia via Toll-like-receptor (TLR) signaling, CD43 - IL-10-producing B cells required additional B-cell activating factor (BAFF)-mediated signals from dendritic cells (DCs) for their differentiation and activation, thereby classifying them as adaptive type Bregs. Importantly, CD43 -, but not CD43 +, IL-10-producing ILB cells displayed bona fide Breg activity by potently suppressing interferon-γ (IFN-γ) production in vitro in an IL-10-dependent manner. Furthermore, a novel CD43 - CD1d hi CD5 + IL-10-producing Breg population was predominantly induced by Chlamydia genital infection in vivo. Correspondingly, mixed bone marrow chimeric mice with B-cell-specific IL-10 deficiency exhibited significantly increased type 1 immune responses, decreased bacterial burden, and reduced oviduct pathology upon infection. Our data demonstrate for the first time a distinct role for CD43 - CD1d hi CD5 + -adaptive Bregs over CD43 + innate counterparts in controlling mucosal responses against intracellular bacterial infection.
Idioma original | English |
---|---|
Páginas (desde-hasta) | 94-106 |
Número de páginas | 13 |
Publicación | Mucosal Immunology |
Volumen | 8 |
N.º | 1 |
DOI | |
Estado | Published - ene. 11 2015 |
Nota bibliográfica
Funding Information:This study was supported by funds from the IWK Health Centre, the Nova Scotia Health Research Foundation, the Canadian Institutes of Health Research (CIHR), and the Canadian Foundation for Innovation (CFI) (to J.W.). J.M.C. was a recipient of IWK Graduate Studentship Award and NSHRF Graduate Scholarship Award. J.W. was a recipient of a CIHR/ NSHRF New Investigator Award. We thank Mr John de Rosenroll and Cynthia Tram for technical assistance and blind assessment of histology slides and Mr Derek Rowter for sorting. We thank Dr Richard Flavell for providing breeding pairs of IL-10GFP mice.
ASJC Scopus Subject Areas
- Immunology and Allergy
- Immunology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't