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Publication : TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4<sup>+</sup> T Cells to T<sub>reg</sub>.

First Author  Dolina JS Year  2020
Journal  Cell Rep Volume  31
Issue  1 Pages  107249
PubMed ID  32268093 Mgi Jnum  J:304691
Mgi Id  MGI:6514537 Doi  10.1016/j.celrep.2020.01.040
Citation  Dolina JS, et al. (2020) TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4(+) T Cells to Treg. Cell Rep 31(1):107249
abstractText  CD4(+) T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8(+) cytotoxic T lymphocyte (CTL) responses, CD4(+) T cells can function as helpers (TH) to amplify magnitude and functionality or as regulatory cells (Treg) capable of profound inhibition. It is unclear what determines differentiation to these phenotypes and whether pathogens provoke alternate programs. We find that, depending on the size of initial dose, Listeria infection drives CD4(+) T cells to act as TH or induces rapid polyclonal conversion to immunosuppressive Treg. Conversion to Treg depends on the TLR9 and IL-12 pathways elicited by CD8alpha(+) dendritic cell (DC) sensing of danger-associated neutrophil self-DNA. These findings resolve long-standing questions regarding the conditional requirement for TH amongst pathogens and reveal a remarkable degree of plasticity in the function of CD4(+) T cells, which can be quickly converted to Tregin vivo by infection-mediated immune modulation.
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