Schistosomal granuloma modulation. I. Schistosoma mansoni worm antigens CAA and CCA prime egg-antigen-induced hepatic granuloma formation

Abstract

Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S.mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.

Experimental models of Schistosoma mansoni infection

“…The interpretation of immune reactions to the eggs is complicated by this previous exposure to antigens, including antigens cross-reactive with egg antigens (Lukacs & Boros 1991). Unisexually infected mice and mice sensitized to many worm antigens are also sensitized to egg antigens and have an augmented and accelerated response to injected eggs , Jacobs et al 1997a, 1998c, in unexplained contrast to the report of Warren and Domingo (1970).…”

Schistosomal granuloma modulation. II. Specific immunogenic carbohydrates can modulate schistosome-egg-antigen-induced hepatic granuloma formation

“…It was demonstrated that live, adult S. mansoni worms could positively modulate egg-antigen-induced hepatic (Van Marck et al 1983;Jacobs et al 1997a) and pulmonary (Cheever et al 1997) granuloma formation. In addition, we recently showed that the gut-derived antigens CCA and CAA were able to prime egg-antigen-induced granuloma formation in the liver (Jacobs et al 1998). These ®ndings are consistent with the observation by Lukacs and Boros (1991) that prepatent S. mansoni infections sensitized for granuloma formation, and by Leptak and Mckerrow (1997) that schistosome egg granulomas and hepatic expression of tumour necrosis factor (TNF-a) are dependent on immune priming during parasite maturation prior to egg deposition.…”

“…Since immunogenic carbohydrates are part of the molecular structure of the gut-associated antigens CCA and CAA, and because these schistosome gut antigens were capable of priming egg-antigen-induced hepatic granuloma formation in vivo (Jacobs et al 1998), we decided to investigate the modulatory capacity of systemically administered LewisX and LNFP-III molecules on egg-antigen-induced hepatic granuloma formation.…”

Granulomatous-like immune reaction and hepatic fibrosis induced bySchistosoma haematobiumimmature worms

“…Monica C. Botelho, 1,2, * Paula A. Oliveira, 3 Paulo Vieira, 1 Maria de Lurdes Delgado, 1 Ligia Lourenço, 3 Carlos Lopes, 4,5 Jose C. Machado 2,6 and Jose M. Correia da Costa 1 exist between the host and the parasite. Parasite stage-specific factors as well as host organ-specific modalities and the genetic background have been identified or implicated in the pathogenesis of schistosomiasis.…”

“…Schistosomal granuloma formation is generally considered to be the result of a delayed-type hypersensitivity response generated by the host toward antigens secreted by tissue-deposited parasite eggs. [3][4][5][6] Schistosomal egg granuloma formation and ensuing hepatic fibrosis are intriguing pathophysiological processes demonstrating the complex interactions that…”