Abstract
Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%–10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-β compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.
Highlights
Among parasitic diseases in tropical and subtropical regions, schistosomiasis is the second most important in terms of socioeconomic and public health impact
Twelve patients were classified as without fibrosis (WF)/incipient fibrosis not excluded (IFNE), thirteen individuals as periportal fibrosis (PPF)/periportal fibrosis (PF), and in the endemic areas we found only four individuals classified as advanced periportal fibrosis (APF)/portal hypertension (PH)
We first evaluated the frequency of T CD4+ lymphocytes expressing IL-4, IL-5, and IL-13 after stimulation with soluble egg antigen (SEA), since these cytokines are the main molecules involved in the pathogenesis of periportal fibrosis related to Schistosoma mansoni infection [19]
Summary
Among parasitic diseases in tropical and subtropical regions, schistosomiasis is the second most important in terms of socioeconomic and public health impact. It affects about 240 million people living in developing countries, especially in rural and peri-urban areas, with an estimated 700 million people at risk worldwide [1]. Unlike the results found in a murine model, where IL-10 plays a key role in controlling the inflammatory response in fibrosis [11], in vitro studies evaluating the frequency of monocytes from individuals with different degrees of periportal fibrosis do not show an increase in IL-10 production [12]. These results suggest that there are other regulatory sources of the inflammatory process observed in the pathogenesis of fibrosis besides IL-10
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