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.

Download full-text


Available from: Richard Strugnell, Apr 28, 2014
68 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Frontiers in Immunology 07/2014; 5:319. DOI:10.3389/fimmu.2014.00319
  • Source
    • "In part, this reflects the complexity of the pathogens, although novel vaccines against papilloma viruses and Varicella zoster combat organisms approaching bacterial levels of complexity (recently reviewed in Stanley, 2008; Abendroth et al., 2010). Intracellular bacterial pathogens appear to be particularly challenging for the immune system, often residing within macrophages or dendritic cells which they modify to best evade immune detection (Bedoui et al., 2010). However, a vaccine that induces a long-lasting high-affinity IgA response can potentially inhibit the initial infection step before bacteria become resident intracellular pathogens. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Intestinal bacteria outnumber our own human cells in conditions of both health and disease. It has long been recognized that secretory antibody, particularly IgA, is produced in response to these microbes and hypothesized that this must play an important role in defining the relationship between a host and its intestinal microbes. However, the exact role of IgA and the mechanisms by which IgA can act are only beginning to be understood. In this review we attempt to unravel the complex interaction between so-called “natural,” “primitive” (T-cell-independent), and “classical” IgA responses, the nature of the intestinal microbiota/intestinal pathogens and the highly flexible dynamic homeostasis of the mucosal immune system. Such an analysis reveals that low-affinity IgA is sufficient to protect the host from excess mucosal immune activation induced by harmless commensal microbes. However, affinity-maturation of “classical” IgA is essential to provide protection from more invasive commensal species such as segmented filamentous bacteria and from true pathogens such as Salmonella typhimurium. Thus a correlation is revealed between “sophistication” of the IgA response and aggressiveness of the challenge. A second emerging theme is that more-invasive species take advantage of host inflammatory mechanisms to more successfully compete with the resident microbiota. In many cases, the function of IgA may be to limit such inflammatory responses, either directly by coagulating or inhibiting virulence of bacteria before they can interact with the host or by modulating immune signaling induced by host recognition. Therefore IgA appears to provide an added layer of robustness in the intestinal ecosystem, promoting “commensal-like” behavior of its residents.
    Frontiers in Immunology 05/2012; 3:100. DOI:10.3389/fimmu.2012.00100
  • Source
    • "Additional illustrations of bacterial mimicry strategies as well as their respective function targets in the host are reviewed elsewhere (Stebbins and Galan, 2001; Shames et al., 2009). Within the last decade, it has become evident that many bacterial effectors target components of the innate immune system (Woolard and Frelinger, 2008; Flannagan et al., 2009; Bedoui et al., 2010; Behr et al., 2010; Harding and Boom, 2010). Given the key role of NF-kB (nuclear factor kB) in the regulation of the innate immunity, it seems logical that microorganisms have evolved complex mechanisms to interfere with NF-kB to evade the immune response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial infections cause substantial mortality and burden of disease globally. Induction of a strong innate inflammatory response is the first common host mechanism required for elimination of the invading pathogens. The host transcription factor, nuclear factor kappa B (NF-κB) is essential for immune activation. Conversely, bacterial pathogens have evolved strategies to interfere directly with host cell signalling by regulating or mimicking host proteins. Given the key role of NF-κB in the host inflammatory response, bacteria have expectedly developed virulence effectors interfering with NF-κB signalling pathways. In this review, we explore the bacterial mechanisms utilized to prevent effective NF-κB signalling, which in turn usurp the host inflammatory response.
    Cellular Microbiology 11/2011; 14(2):155-67. DOI:10.1111/j.1462-5822.2011.01719.x · 4.92 Impact Factor
Show more