Abstract
Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.
Highlights
Alveolar Echinococcosis (AE) of man can develop following the ingestion of eggs of Echinococcus multilocularis
IL-5 is the predominant cytokine expressed by Peripheral Blood Mononuclear Cells (PBMC) in AE patients [5], and Th2type IL-3, IL-5, and IL-10 were enhanced in severely ill AE patients [6,7,8] while E. multilocularis antigen-induced IFN-γ and spontaneous IL-12 production were decreased [9, 10]
Within the AE patient group, lowest concentrations of IL-17B were detected in cured cases of AE, while highest concentrations were observed in progressive cases
Summary
Alveolar Echinococcosis (AE) of man can develop following the ingestion of eggs of Echinococcus multilocularis. In some cases of human AE, a spontaneous healing of the disease was observed [1, 3] Such abortive cases are characterized by calcified parasite lesions suggesting the generation of immune responses which are able to limit parasite growth in humans [4]. Previous studies have shown that Th1- and Th2type immune responses might be important for clearance of the infection and are associated with the chronic and progressive course of disease [4]; knowledge about the crucial determinants which limit parasite growth and disease progression remains scarce. IL-12 and IFN-γ inhibited larval growth and metacestode dissemination in E. multilocularis-infected mice [11, 12], while the application of IFN-γ stopped disease progression in an AE patient [13]
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