Differential responsiveness of humans with early-stage schistosomiasis haematobium to Schistosoma haematobium soluble adult-worm and egg antigens

Abstract

Schoolchildren (7-8 years old) infected with Schistosoma haematobium were tested for lymphocyte proliferative responses, in vitro granuloma formation (IVGF), and cytokine release in T-cell Western assays and for serum antibody reactivity by enzyme-linked immunosorbent assay (ELISA) and immunoblotting against S. haematobium soluble adult-worm (SAWA) and egg (SEA) antigens. The lymphoproliferative response rate of individual subjects against 10 SAWA and 15 SEA electroseparated bands ranged from 0 to 33% and from 11 to 66%, respectively. The SAWA bands essentially failed to elicit significant IVGF, in contrast to the SEA bands, all of which were capable of inducing IVGF from peripheral blood mononuclear cells (PBMC) of 30-80% of individual donors. The exclusive ability of SEA bands to induce IVGF could not be attributed to selective release of interleukin 2 (IL-2), IL-4, or interferon-gamma, as SEA and SAWA bands were capable of eliciting release of a similar array of cytokines in supernatants of 4-day PBMC cultures. The antibody response to SEA was stronger than that to SAWA, yet the proportion of SAWA bands binding humoral antibodies of individual donors was significantly larger than that observed for SEA. The study thus suggests that humans with early-stage S. haematobium infection respond poorly to SAWA but mount strong cellular immune responses to SEA that result in granuloma and antibody formation.

Increased Prevalence of Leukocytes and Elevated Cytokine Levels in Semen fromSchistosoma haematobium–Infected Individuals

“…The retained ova in the host tissue evokes a delayed-hypersensitivity granulomatous T cell-mediated immune response mediated by soluble egg antigens, resulting in an accumulation of eosinophils, macrophages, and lymphocytes and thus forming the classic Schistosoma granuloma [34]. The cytokines involved in the formation of granuloma in schistosomiasis infection include TNF-a, IL-2, IL-4, and IL-5, whereas IFN-g, IL-10, and IL-12 are known for their immune modulating role [35][36][37][38].…”

A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology

“…In human disease, S. haematobium infection proceeds through cercarial skin invasion, systemic schistosomular circulation and maturation, adult worm mating within the bladder venous plexus, and egg deposition/excretion [67]. This complex natural history provides potential exposure to a broad range of antigens; however, the relative brevity of cercarial persistence and schistosomular circulation (hours to days [68]) and the relative lack of antigenicity of adult worms [69] may limit their contribution to long-term immunopathology. The unexcreted schistosome egg, in contrast, may persist for many years in host tissues and is a well-established, potent immunogen (e.g., soluble egg antigen or SEA [69]).…”

Human T- and B-Cell Responses toSchistosoma mansoniRecombinant Glyceraldehyde 3-Phosphate Dehydrogenase Correlate with Resistance to Reinfection withS. mansoniorSchistosoma haematobiumafter Chemotherapy

“…Peripheral blood (10 ml) was obtained from each subject, and peripheral blood mononuclear cells (PBMC) and plasma were prepared as described elsewhere (1,18,19).…”

“…SAWA and soluble egg antigens (SEA) were prepared from worms and eggs, respectively, of S. mansoni (SAWA m and SEA m ) and S. haematobium (SAWA h and SEA h ) (Egyptian strain; Schistosome Biological Supply Centre, Cairo, Egypt) as described elsewhere (1,18,19).…”