Chapter 41 : The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity

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Chronic inflammatory disorders (CIDs) encompass classical autoimmune diseases, in which the immune system recognizes and attacks host tissue, atopic and allergic diseases, as well as other chronic inflammatory syndromes (psoriasis, sarcoidosis, Crohn's disease). Many types of organisms appear to be involved, and their nature and the mechanisms they activate to prevent or mitigate CIDs are discussed in this chapter. Immune responses either contribute to differentiation of antibacterial effector mechanisms or may trigger or exacerbate chronic inflammatory disorders by molecular mimicry or bystander activation (CID). There are several mechanisms by which microbial encounter may lead to CID. First, the pathogen itself may persist and chronically trigger an inflammatory response. Second, the infectious agent may exhibit structural elements that are similar enough in three-dimensional conformation to self-antigen that the pathogen acts as a self-mimic. This chapter also provides representative examples of CIDs promoted by selected bacterial or parasitic infections to illustrate some of the relevant molecular and immunological pathways involved. Atherosclerosis is now generally classified as a chronic inflammatory disease. Experimental immunization with N. aromaticivorans can induce autoreactive antimitochondrial antibodies (AMA) and chronic (primary biliary cirrhosis) PBC-like T-cell-mediated autoimmunity against small bile ducts in a murine model of PBC.

Citation: Ehlers S, Rook G. 2011. The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity, p 521-536. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch41
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This simplified scheme shows possible immune responses to microbial challenge. They either contribute to differentiation of antibacterial effector mechanisms (top) or may trigger or exacerbate chronic inflammatory disorders by molecular mimicry or bystander activation (CID) (bottom).

Citation: Ehlers S, Rook G. 2011. The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity, p 521-536. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch41
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Image of FIGURE 2

Epidemiological studies and laboratory screening for immunoregulatory properties have highlighted organisms that were present throughout the evolution of the mammalian immune system, but are relatively depleted from the modern environment. These include organisms that undergo orofecal transmission, ubiquitous environmental organisms (i.e., “pseudocommensals” in mud, untreated water, and fermented foods), helminths, and gut microbiota. In wealthy developed countries where exposure to these is diminished, CID may develop in individuals with genetic predisposition to dysregulation of Th1/Th17 or Th2 effector mechanisms. This is a classical geneenvironment interaction.

Citation: Ehlers S, Rook G. 2011. The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity, p 521-536. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch41
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Examples of molecular mimicry driving autoimmune inflammation

Citation: Ehlers S, Rook G. 2011. The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity, p 521-536. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch41
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Some of the bacteria and helminths shown to inhibit chronic inflammatory disorders in animals and humans

Citation: Ehlers S, Rook G. 2011. The Role of Bacterial and Parasitic Infections in Chronic Inflammatory Disorders and Autoimmunity, p 521-536. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch41

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