Abstract
Soluble flagellin (sFliC) from Salmonella Typhimurium (STm) can induce a Th2 response to itself and coadministered antigens through ligation of TLR5. These properties suggest that sFliC could potentially modulate responses to Th1 antigens like live STm if both antigens are given concurrently. After coimmunization of mice with sFliC and STm there was a reduction in Th1 T cells (T‐bet+IFN‐γ+ CD4 T cells) compared to STm alone and there was impaired clearance of STm. In contrast, there was no significant defect in the early extrafollicular B‐cell response to STm. These effects are dependent upon TLR5 and flagellin expression by STm. The mechanism for these effects is not related to IL‐4 induced to sFliC but rather to the effects of sFliC coimmunization on DCs. After coimmunization with STm and sFliC, splenic DCs had a lower expression of costimulatory molecules and profoundly altered kinetics of IL‐12 and TNFα expression. Ex vivo experiments using in vivo conditioned DCs confirmed the effects of sFliC were due to altered DC function during a critical window in the coordinated interplay between DCs and naïve T cells. This has marked implications for understanding how limits in Th1 priming can be achieved during infection‐induced, Th1‐mediated inflammation.
Highlights
DCs can efficiently capture, process, and present antigen to T cells in the T zones of secondary lymphoid tissues such as the spleen
Th1 responses are induced by intracellular bacteria such as Salmonella enterica serovar Typhimurium (STm), Th17 responses are characteristic of pneumococcal infection and Th2 responses are observed after exposure to antigens such as helminths and alum-precipitated proteins such as OVA
T cells were isolated and MACS-enriched to transfer 107 EYFP T cells into WT mice, 24 h posttransfer mice were nonimmunized or immunized with 5 × 105 STm, 20 μg sFliC, or both, activation was evaluated on EYFP+ T cells. (Top) Representative plots show the expression of CD69 on EYFP+TCRαβ+CD4+ cells frequency and the absolute number of CD69+EYFP+ T cells at
Summary
DCs can efficiently capture, process, and present antigen to T cells in the T zones of secondary lymphoid tissues such as the spleen. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. The direction of Th-cell differentiation is influenced by the nature of the antigen. Th1 responses are induced by intracellular bacteria such as Salmonella enterica serovar Typhimurium (STm), Th17 responses are characteristic of pneumococcal infection and Th2 responses are observed after exposure to antigens such as helminths and alum-precipitated proteins such as OVA. T-bet-deficient mice generate T-cell responses to STm but fail to clear the bacteria due to an impairment in Th1 development [2, 4,5,6,7]
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