Recognition of Salmonella by Dectin‐1 induces presentation of peptide antigen to type B T cells

Abstract

Type B T cells recognize peptide–MHC class II (pMHCII) isoforms that are structurally distinct from those recognized by conventional type A T cells. These alternative type B conformers result from peptide loading in the absence of HLA-DM. Type A conformers are more stable than type B pMHCII conformers but bind the same peptide in the same register. Here, we show that interaction of Salmonella Typhimurium with bone marrow derived dendritic cells (BMDCs) isolated from C3H/HeNCr1 mice results in enhanced presentation of peptide Ag to type B T cells. The effect could be mimicked by purified PAMPs, the most potent of which were curdlan and zymosan, β-(1,3)-glucan-containing polymers that are recognized by Dectin-1. Blocking of Dectin-1 with Ab and laminarin inhibited the induction of the type B T-cell response by BMDCs, confirming its role as a PRR for S. Typhimurium. Splenic DCs (sDCs) expressed Dectin-1 but were refractive to the induction of type B responses by S. Typhimurium and curdlan. Type B T cells have been shown to escape thymic tolerance and to transfer pathology in an autoimmune disease model. The induction of type B responses by gram-negative bacteria provides a mechanism by which autoreactive T cells may be produced during infection.

Flexible Signaling of Myeloid C-Type Lectin Receptors in Immunity and Inflammation

“…Dectin-1 triggers a response after sensing infectious agents, such as diverse fungi and mycobacteria ( 118 ), Salmonella typhimurium ( 119 ) or Leishmania infantum ( 120 ). Dectin-1 may also promote proinflammatory signals following the detection of endogenous factors, such as vimentin from atherosclerotic plaques ( 121 ), galectin-9 from pancreatic carcinoma ( 122 ), or N-glucans on tumor cells ( 123 ).…”

DECTIN-1: A modifier protein in CTLA-4 haploinsufficiency

“…DECTIN-1 is a well-described PRR with crucial functions in anti-fungal immunity through the recognition of β-glucans, e.g., zymosan, a naturally occurring component of the cell wall of Saccharomyces cerevisiae ( 14 ). DECTIN-1 can also recognize bacterial antigens including Salmonella ( 15 , 16 ). In contrast with this role in anti-microbial immunity, DECTIN-1 recognition of commensal species can induce tolerogenic immune responses by promoting differentiation of regulatory antigen-presenting cells (DCs and macrophages) that help maintain gut symbiosis ( 14 , 17 , 18 ).…”

Unconventional T‐cell recognition of an arthritogenic epitope of proteoglycan aggrecan released from degrading cartilage

“…21 Infection of mice with Salmonella typhimurium has also been shown to bias HEL presentation by dendritic cells (DC) towards a type B T-cell response by a Dectin-1-dependent mechanism. 22,23 Furthermore, mice expressing endogenous HEL were used to show that type B T cells escape negative selection during thymic development in vivo, whereas the majority of type A T cells are deleted, 24 creating a scenario in which self-reactive type B T cells could persist in peripheral lymphoid organs. Type B T cells specific for the autoepitope of insulin 9-23/A g7 have been cloned from pancreatic islets, the site of autoimmune damage, 16 and so are localized where they could play a role in autoimmunity.…”

“…Alternatively, exogenous peptides were shown to bind to mature MHC II molecules in early endosomes or at the APC surface in the absence of functional H2‐DM, resulting in formation of a mixture of type A and type B T‐cell conformers . Infection of mice with Salmonella typhimurium has also been shown to bias HEL presentation by dendritic cells (DC) towards a type B T‐cell response by a Dectin‐1‐dependent mechanism . Furthermore, mice expressing endogenous HEL were used to show that type B T cells escape negative selection during thymic development in vivo , whereas the majority of type A T cells are deleted, creating a scenario in which self‐reactive type B T cells could persist in peripheral lymphoid organs.…”