Chapter 28 : Pathogenesis of Helminth Infections

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Acute helminth infections in inappropriate hosts can also cause severe febrile and debilitating illnesses. In the murine model of Schistosoma mansoni, parasites reside in mesenteric veins where they lay hundreds of eggs per day 4 to 5 weeks postinfection. Some eggs are trapped in the microvasculature of the liver and gut, where they induce a vigorous granulomatous response. Subsequently, fibrosis and portal hypertension develop. Consequently, much of the symptomatology of schistosomiasis is attributed to the egg-induced granulomatous response. To formally elucidate the function of macrophage-specific Arg1 mice expressing a macrophage/ neutrophil specific deletion of ( ;) were investigated during a study. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages ( ;), chronically infected ; mice died at an accelerated rate. The increased mortality was not due to excess nitric oxide (NO) production. However, liver sections from chronically infected ; mice showed a significant increase in granulomatous inflammation, liver fibrosis, and portal hypertension. In the past decade, however, macrophages have emerged as central to all aspects of antihelminth immunity, including pathology, protection, and regulation. Finally, by increasing our understanding of the “normal” functions of AAM π during helminth infection, we can better understand the circumstances in which they act inappropriately, such as with allergic asthma, fibrosis, and some forms of cancer. This will hopefully lead to the development of strategies to control the negative consequences of Th2-mediated immune dysregulation with implications for chronic noninfectious diseases, as well as helminth induced pathology.

Citation: Wynn T, Allen J. 2011. Pathogenesis of Helminth Infections, p 347-359. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch28
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Distinct forms of lethal pathology develop when Th1/Th17 or Th2 responses dominate during infection. In murine schistosomiasis, when the immune response to the egg deposited in tissues (e.g., gut, liver, bladder) is skewed to Th1, Th17, or Th2-type cytokine responses, distinct forms of lethal immunopathology develop. When Th1/Th17 responses predominant, particularly in the acute stage of the disease or in animals genetically predisposed to develop stronger Th1/Th17 responses, infected mice suffer from severe acute morbidity and mortality, which is associated with the development of severe inflammation in the gut and liver, hepatotoxicity, and endotoxemia with minimal liver fibrosis. In contrast, when Th2 responses prevail, mice survive acute infection, but the persistent Th2 response contributes to the development of liver fibrosis, portal hypertension, development of collateral blood vessels, hematemesis, and death in the chronic stages of infection.

Citation: Wynn T, Allen J. 2011. Pathogenesis of Helminth Infections, p 347-359. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch28
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The role of L-arginine, cationic amino acid transporters, and alternatively activated macrophages in the pathogenesis of helminth infection. Alternatively activated macrophages expressing arginase-1 suppress the Th2 response in helminth infection by competing with CD4 T cells and fibroblasts for L-arginine. In contrast, classically activated macrophages express iNOS, which is important for the development of nitric oxide that participates in the killing on intracellular pathogens. The iNOS and Arg1 pathways also cross-regulate each other.

Citation: Wynn T, Allen J. 2011. Pathogenesis of Helminth Infections, p 347-359. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch28
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