TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4+ T Cells to Treg

Dolina, Joseph S.; Lee, Joey; Griswold, Ryan Q.; Labarta-Bajo, Lara; Kannan, Sumetha; Greenbaum, Jason A.; Idrissi, Nawal Bahia El; Pont, Margot J.; Croft, Michael; Schoenberger, Stephen P.

doi:10.1016/j.celrep.2020.01.040

Cited by 11 publications

(10 citation statements)

References 85 publications

(100 reference statements)

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“…Monocyte-derived DCs stimulated with TLR4 and TLR7/8 ligands induce naive allogeneic CD4 + T cells to secrete IL-10 and IFN-γ sequentially and eventually IL-17A ( 107 ). The activation of TLR9 and IL-12 pathways in CD8α + DCs can drive CD4 + T cells to act as Th cells or induce rapid polyclonal conversion to immunosuppressive Treg during Listeria infection ( 108 ). Interestingly, although all TLRs on DCs are able to induce CD8 + T cell activation in vitro , the abilities of surface and endosomal TLRs to activate CD8 + T cells might be different in vivo .…”

Section: Tlr-mediated Regulation Of Apcsmentioning

confidence: 99%

Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

et al. 2022

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Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host’s defense against infectious diseases, autoimmune diseases, and cancer.

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Section: Tlr-mediated Regulation Of Apcsmentioning

confidence: 99%

Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

et al. 2022

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“… 26 There is accumulative evidence suggesting the interactions between DNA and CD4 + T cells. Recent studies have shown the conversion of conventional CD4 + T cells into Tregs due to exposure of self‐DNA in Listeria infection 61 and self‐DNA induced stimulation of activated CD4 + T cells. 62 These studies point towards some of the implications of this unexplored interaction of adaptive immune cells and innate immune triggers in health and disease.…”

Section: Discussionmentioning

confidence: 99%

TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells

Sharma

Kumar

et al. 2022

Scand J Immunol

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CpG Oligodeoxynucleotides (ODNs) are established TLR9 ligands; however, their functional responses in CD4+ T cells are believed to be independent of TLR9 and MyD88. We studied ligand-receptor interactions of ODN 2216 and TLR9 in human CD4+ T cells and assessed their consequences in terms of TLR9 signalling and cell phenotype. We demonstrated that the uptake of ODN 2216, a synthetic TLR9 agonist, is controlled by TLR9 signalling molecules and results in an increase in the expression of TLR9 signalling molecules, regulated via a feedback mechanism. Next, the uptake of ODN 2216 resulted in TLR9 signalling dependent but MyD88 independent increase in expression of TGF-β. Finally, ODN 2216 treated CD4+ T cells showed an anti-inflammatory phenotype that was similar to Th3 type of regulatory T cells. These Th3-like cells were able to suppress the proliferation of untreated CD4+ T cells. Collectively, our results demonstrate a direct How to cite this article: Sharma RK, Sharma J, Kumar R, et al. TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells.

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“…In practice, however, some PRRs have not been proven to bind directly to cryptococcal cells, which makes it important to carefully consider whether they are true PRRs. Because PRRs also recognize the so-called alarmins, including self-DNA, HMGB1, and S100A9, they can also respond to the alarmins that emerge after response to a cryptococcal stimuli [39][40][41][42]. Even in this case, because cytokine production can be reduced after cryptococcal stimulation in PRRs-deficient cells, it may not be possible to accurately determine whether the PRRs recognize cryptococcus-induced alarmins or cryptococcal cells itself.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus gattii evades CD11b‐mediated fungal recognition by coating itself with capsular polysaccharides

et al. 2021

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Cryptococcus gattii is a capsular pathogenic fungus causing life-threatening cryptococcosis.Although the capsular polysaccharides (CPs) of C. gattii are considered as virulence factors, the physiological significance of CP biosynthesis and of CPs themselves is not fully understood, with many conflicting data reported. First, we demonstrated that CAP gene deletant of C. gattii completely lacked capsule layer and its virulence, and that the strain was susceptible to host-related factors including oxidizing, hypoxic, and hypotrophic conditions in vitro. Extracellular CPs recovered from culture supernatant bound specifically to C. gattii acapsular strains, not to other fungi and immune cells, and rendered them the immune escape effects. In fact, dendritic cells (DCs) did not efficiently uptake the CP-treated acapsular strains, which possessed no visible capsule layer, and a decreased amount of phosphorylated proteins and cytokine levels after the stimulation. DCs recognized C. gattii acapuslar cells via an immune receptor CD11b-and Syk-related pathway; however, CD11b did not bind to CP-treated acapsular cells. These results suggested that CPs support immune evasion by coating antigens on C. gattii and blocking the interaction between CD11b and C. gattii cells. Here, we describe the importance of CPs in pathogenicity and immune evasion mechanisms of C. gattii.

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TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4+ T Cells to Treg

Cited by 11 publications

References 85 publications

Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells

Cryptococcus gattii evades CD11b‐mediated fungal recognition by coating itself with capsular polysaccharides

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