Pathogenesis of Helminth Infections

Abstract

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 Arg1 (Arg1 flox/flox ;lysMcre) were investigated during a study. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages (Arg1 flox/flox;lysMcre), chronically infected Arg1 flox/flox;lysMcre mice died at an accelerated rate. The increased mortality was not due to excess nitric oxide (NO) production. However, liver sections from chronically infected Arg1 flox/flox;lysMcre 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.