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Adaptive Immunity Induces Tolerance to Flagellin by Attenuating TLR5 and NLRC4-Mediated Innate Immune Responses
- Source :
- Frontiers in Cellular and Infection Microbiology, Vol 9 (2019)
- Publication Year :
- 2019
- Publisher :
- Frontiers Media S.A., 2019.
-
Abstract
- The host immune system is constantly exposed to diverse microbial ligands, including flagellin (FliC; a ligand for TLR5 and NLRC4) and lipopolysaccharide (LPS; a ligand for TLR4), which could induce immune tolerance to subsequent exposure. Herein, we investigated the extent to which FliC induces self-tolerance in vivo and the role of adaptive immunity in mediating such effect. Mice pre-treated with FliC displayed attenuated serum keratinocyte-derived chemokine (KC), interleukin (IL)-6 and IL-18 responses to secondary challenge of FliC. A negative correlation was observed between high anti-FliC titer and reduced KC, IL-6, and IL-18 responses upon FliC re-challenge in WT mice, but not Rag1KO mice, suggesting that adaptive immunity could tolerize TLR5 and NLRC4. However, administration of LPS during FliC pre-treatment impaired the generation of anti-FliC antibodies and resulted in a partial loss of self-tolerance to FliC re-challenge. These findings may be relevant in the context of bacterial infection, as we observed that anti-FliC response are protective against systemic infection by Salmonella typhimurium. Taken together, our study delineates a distinct co-operative and reciprocal interaction between the innate and adaptive arms of immunity in modulating their responses to a bacterial protein.
Details
- Language :
- English
- ISSN :
- 22352988
- Volume :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Cellular and Infection Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.69df33d0946d4b8d8b57ccb7d322dab3
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fcimb.2019.00029