Different Bacterial Pathogens, Different Strategies, Yet the Aim Is the Same: Evasion of Intestinal Dendritic Cell Recognition

Department of Microbiology and Immunology, University of Melbourne, Gate 11, Royal Parade, Parkville 3010, Victoria, Australia. E-mail address:
The Journal of Immunology (Impact Factor: 4.92). 03/2010; 184(5):2237-42. DOI: 10.4049/jimmunol.0902871
Source: PubMed


Given the central role of intestinal dendritic cells (DCs) in the regulation of gut immune responses, it is not surprising that several bacterial pathogens have evolved strategies to prevent or bypass recognition by DCs. In this article, we will review recent findings on the interaction between intestinal DCs and prototypical bacterial pathogens, such as Salmonella, Yersinia, or Helicobacter. We will discuss the different approaches with which these pathogens seek to evade DC recognition and subsequent T cell activation. These diverse strategies span to include mounting irrelevant immune responses, inhibition of Ag presentation by DCs, and stretch as far as to manipulate the Th1/Th2 balance of CD4(+) T cells in the bacteria's favor.

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Available from: Richard Strugnell, Apr 28, 2014
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    • "By demonstrating that T cell help amplifies innate signals, our work identifies an important mechanism through which CD4 + T cells endow DCs with optimal capacities to prime CD8 + T cells when danger signals alone are insufficient to achieve this. This is highly relevant to CD8 + T cell priming in infections where microbial immune evasion strategies (Bedoui et al., 2010) or restriction of pathogen replication to peripheral tissues (vanLint et al., 2004) limit the availability of danger signals at sites of T cell priming. Similarly, T-cell-help-induced amplification of innate pathways likely contributes to tumor-specific CD8 + T cell priming, which often is associated with limited exposure to danger signals. "
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    ABSTRACT: DCs often require stimulation from CD4+ T cells to propagate CD8+ T cell responses, but precisely how T cell help optimizes the priming capacity of DCs and why this appears to differ between varying types of CD8+ T cell immunity remains unclear. We show that CD8+ T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4+ T cells to provide IL-15. This was not an additive effect but resulted from CD4+ T cells amplifying DC production of IL-15 in response to IFN-α/β. We also observed that increased innate stimulation reversed the helper dependence of CD8+ T cell priming and that the innate stimulus, rather than the CD4+ T cells themselves, determined how “help’” was integrated into the priming response by DCs. These findings identify T cell help as a flexible means to amplify varying suboptimal innate signals in DCs.
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    • "The stimulatory signals required to elicit local IFN-γ from effector T cells in tissues could potentially involve cognate stimulation via peptide/MHC complexes on the surface of infected cells or resident dendritic cells (Figure 1). However, many intracellular pathogens have evolved strategies that prevent MHC presentation of microbial peptides or down-regulate surface MHC expression on infected cells (46, 47). While down-regulation of MHC class-I is often discussed as a viral evasion strategy (48), Salmonella have also been reported to reduce expression of MHC class-II of antigen-presenting cells (49). "
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    ABSTRACT: Intra-macrophage bacterial infections cause significant morbidity and mortality in both the developed and developing world. Protective host immune responses to these infections initially requires the activation and expansion of pathogen-specific CD4 Th1 cells within lymphoid tissues and subsequent relocation of these effector cells to sites of infection. After entering infected tissues, the elicitation of Th1 bactericidal activity can be triggered by cognate or non-cognate signals that are delivered by locally infected antigen-presenting cells and innate cells. However, the contribution of non-cognate stimulation to the resolution of bacterial infection remains poorly understood, especially in the context of a Th1 response. Here, we review the current data on Th1 cell activation and expansion in mouse models of Salmonella and Chlamydia infection and discuss the potential role of non-cognate Th1 cell stimulation in these disease models. Greater understanding of this pathway of T cell activation may lead to the design of therapeutics or vaccines to combat intra-macrophage pathogens.
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