Survival strategy of Echinococcus multilocularis in the human host.
As exemplified by "aborted" calcified liver lesions commonly found in patients from endemic areas, Echinococcus multilocularis metacestodes develop only in a minority of individuals exposed to infection with the papasite. Clinical research has disclosed some aspects of the survival strategy of E. multilocularis in human hosts. Clinical observations in liver transplantation and AIDS suggest that suppression of cellular/Th1-related immunity increases disease severity. Most of the studies have stressed a role for CD8+ T cells and for Interleukin-10 in the development of tolerance. A spontaneous secretion of IL-10 by the PBMC seems to be the immunological hallmark of patients with progressive forms of alveolar echinococcosis (AE). IL-10-induced inhibition of effector macrophages, but also of antigen-presenting dendritic cells, may be operating and allowing parasite growth and survival. The genetic correlates of susceptibility to infection with E. multilocularis are clearer in humans than in the mouse model. A significant link between MHC polymorphism and clinical presentation of AE has been shown, and the spontaneous secretion of IL-10 in patients with a progressive AE is higher in patients with the HLA DR3+, DQ2+ haplotype. Clustering of cases in certain families, in communities otherwise exposed to similar risk factors, also points to immuno-genetic predisposition factors that may allow the larva to escape host immunity more easily. The first stage of larval development may be crucial in producing "danger signals" stimulating the initial production of cytokines. Therapeutic use of Interferon alpha is an attempt to foil the survival strategy of E. multilocularis.
Vuitton
Dominique Angèle
DA
WHO Collaborating Centre for Prevention and Treatment of Human Echinococcosis, Université de Franche-Comté and University Hospital, Besançon, France. Dominique.Vuitton@univ-fcomte.fr
Zhang
Shao Ling
SL
Yang
Yurong
Y
Godot
Véronique
V
Beurton
Isabelle
I
Mantion
Georges
G
Bresson-Hadni
Solange
S
D000818:Animals; D004444:Echinococcosis, Hepatic / Q000235:genetics / Q000276:immunology / Q000469:parasitology*; D048210:Echinococcus multilocularis / Q000254:growth & development / Q000472:pathogenicity*; D006790:Host-Parasite Interactions; D006801:Humans; D007108:Immune Tolerance