Phenotypic Characterization of CD4+ T Lymphocytes in Periportal Fibrosis Secondary to Schistosomiasis.

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-ß 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.

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis.

Coinfection with leishmaniasis and schistosomiasis has been associated with increased time to healing of cutaneous lesions of leishmaniasis. The objective of this study was to evaluate the effect of Leishmania braziliensis infection on co-cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes from patients with schistosomiasis and patients with cutaneous leishmaniasis. MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic beads, infected with L. braziliensis, and co-cultured with autologous lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10 receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on lymphocytes were evaluated by flow cytometry. The production of the cytokines IL-10, TNF, IL-12p40, and IFN-γ were evaluated by sandwich ELISA of the culture supernatant. The infectivity evaluation was performed by light microscopy after concentration of cells by cytospin and Giemsa staining. It was observed that the frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR were smaller in the group of patients with schistosomiasis compared to the group of patients with leishmaniasis. On the other hand, the frequency of IL-10R on MoDCs was higher in patients with schistosomiasis than in patients with leishmaniasis. CD4+ and CD8+ T lymphocytes from patients with schistosomiasis presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the supernatants of co-cultures from individuals with schistosomiasis compared to those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-γ were lower in the group of individuals with schistosomiasis. Regarding the frequency of MoDCs infected by L. braziliensis after 72h in culture, it was observed that higher frequencies of cells from patients with schistosomiasis were infected compared to cells from patients with leishmaniasis. It was concluded that MoDCs from patients with schistosomiasis are more likely to be infected by L. braziliensis, possibly due to a lower degree of activation and a regulatory profile.