Artikel
Host defense versus immunosuppression: Male and female Schistosoma mansoni differentially impact the host’s immune system
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Veröffentlicht: | 8. Oktober 2018 |
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Gliederung
Text
Schistosomiasis remains a major cause of morbidity and mortality, and in the tropics and subtropics, in particular, infection rates are high [1]. The efficacy of anthelmintic therapy is limited since it has no effect on immature parasite stages and does not prevent re-infection. The root cause of the disease is a granulomatous hypersensitivity reaction to parasite eggs entrapped within the intestinal wall and small liver sinusoids. This reaction is mainly caused by CD4+ T cells of the subtype 2 (TH2) and alternatively activated macrophages, which initiate tissue repair but also hepatic fibrosis leading to portal hypertension and its clinical sequelae, ascites and esophageal varices [2].
There are two basic options to reduce egg-induced pathology during Schistosoma spp. infection:
- 1.
- achieving resistance to reinfection, or
- 2.
- dampening down granulomatous hyperreactivity [3].
Mice that were primarily infected with female schistosomes prior to a secondary infection with cercariae of both sexes display a diminished TH2 immune response resulting in reduced granuloma size, hepatic fibrosis, and disease progression [4]. This protection is mediated by the upregulation of CTLA4 which is known to suppress T cell responses. In addition, primary infection with female schistosomes suppresses early innate immune responses against invading cercariae in the skin. In contrast, primary infection with male schistosomes triggers strong innate immune reactions in the skin, resulting in a reduction of worm and egg burden in the liver [5].
We, therefore, propose that the female worm is a neglected player in the dampening down of the host’s immune defense mechanisms and is a promising target for new immune modulatory strategies.
References
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