Mramba Nyindo

Repeated Exposure Induces Periportal Fibrosis in Schistosoma mansoni-Infected Baboons: Role of TGF-β and IL-4

Recently, we observed that repeated Schistosoma mansoni infection and treatment boost Th2-associated cytokines and TGF-β production in baboons. Other studies have shown that some chronically infected baboons develop hepatic fibrosis. Because TGF-β, IL-2, and IL-4 have been shown to participate in development of fibrosis in murine schistosomiasis, the present study examined whether repeated exposure stimulates hepatic fibrosis in olive baboons. To test this hypothesis, animals were exposed to similar numbers of S. mansoni cercariae given once or repeatedly. After 19 wk of infection, animals were cured with praziquantel and reinfected once or multiple times. Hepatic granulomatous inflammation and fibrosis were assessed from serial liver biopsies taken at weeks 6, 9, and 16 after reinfection and egg Ag (schistosome egg Ag)-specific cytokine production by PBMC were measured simultaneously. Periportal fibroblast infiltration and extracellular matrix deposition (fibrosis), angiogenesis, and biliary duct hyperplasia developed in some animals. The presence and amount of fibrosis directly correlated with the frequency of exposure. Fibrosis was not associated with adult worm or tissue egg burden. The amount of fibrosis correlated with increased schistosome egg Ag-driven TGF-β at 6, 9, and 16 wk postinfection (rs = 0.9, 0.8, and 0.54, respectively, all p < 0.01) and IL-4 production (p = 0.02) at 16 wk postinfection and not IFN-γ, IL-2, IL-5, or IL-10. These data suggest that repeated exposure is a risk factor for periportal fibrosis by a mechanism that primes lymphocytes to produce increased levels of profibrotic molecules that include TGF-β and IL-4.

Ultrastructural changes in salivary glands of tsetse, Glossina morsitans morsitans, infected with virus and rickettsia-like organisms.

Electron microscope observations on enlarged hypertrophied salivary glands dissected from adult laboratory-reared male Glossina morsitans morsitans show a concurrent infection of the salivary gland tissue with rod-shaped virus particles and intracellular rickettsia-like organisms. The latter are found intracellular in the epithelium and in the gland lumen enclosed within lytic zones. The virus particles are found within the degenerating cytoplasm, nuclei, and lumen of the cell where they are especially numerous. Stratified epithelium and gland enlargement are a prominent feature of the infection. These observations suggest that biological associations between salivary gland tissue and diverse microbes may be more common than formerly recognized. The microbes appear to cause damage to salivary gland cells, causing hyperplasia which assumes pathologic proportions.

Acute schistosomiasis mansoni in the baboon Papio anubis gives rise to goblet-cell hyperplasia and villus atrophy that are modulated by an irradiated cercarial vaccine

Abstract A histopathology study of the intestines of four Kenyan baboons (Papio anubis) infected by 800 cercariae of Schistosoma mansoni and euthanized at 10 weeks postinfection was done. The pathology was compared with that of four baboons first vaccinated with 10,000 irradiated cercariae and then challenged 8–10 weeks later with the same number of cercariae. Two baboons that were neither vaccinated nor challenged were used as controls. On postmortem examination, multifocal to coalescing granulomatous inflammatory responses to the eggs in the submucosa of the terminal ileum and colon were seen in all baboons exposed to the parasite. The mean numbers of goblet cells detected per villus at 20 cm from the pylorus were 12.8 ± 2.6, 30.4 ± 6.6, and 20.2 ± 3.7 in the two uninfected baboons, the infected unvaccinated baboons, and the vaccinated and challenged baboons, respectively. Mild to total villus atrophy was present in all eight baboons exposed to the parasite. These lesions, which were less marked in infected but vaccinated baboons, may contribute to the clinical signs seen in acute simian schistosomiasis mansoni.

Trypanosoma brucei: Infectivity and immunogenicity of cultured parasites

Trypanosoma brucei brucei, derived from the salivary glands of infected tsetse flies (Glossina morsitans morsitans) and maintained in culture for over 4 years, were infective to both albino rats and tsetse flies. Virulence was markedly enhanced during the first passage in albino rats or tsetse flies. Irradiated cultured trypanosomes induced immunity to homologous challenge but not to tsetse fly or blood-induced challenge with the same stock.