Characterization of memory T cells in individuals resistant to Schistosoma mansoni infection.

Schistosomiasis affects about 240 million people worldwide and is estimated that about 700 million people live in areas at risk of infection. In the context of immune response associated with infection by Schistosoma mansoni, the role of memory T cells is not well understood. AIM: To evaluate the frequency of memory CD4+ and CD8+ T cells from individuals resistant and susceptible to Schistosoma mansoni infection. METHODS AND RESULTS: We selected individuals with low (resistant) and high (susceptible) parasite burden using databases generated during previous studies carried out in the same endemic area. The cell surface markers were performed using flow cytometry. In this study, the resistant individuals showed an increase in the CD4+ memory T-cell pool associated with an increase in the central memory cell (TCM) and a decrease in the effector memory cell (TEM ). Individuals susceptible to infection had higher frequencies of effector memory cells compared to resistant individuals. CONCLUSIONS: These data suggest that resistance to S mansoni infection may be associated with an increase in the number of CD4+ memory T cells and susceptibility to infection is associated with a decrease in the central memory cell as well as high proportions of effector memory cells.

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.

Monocyte subsets in schistosomiasis patients with periportal fibrosis.

A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), and nonclassical (CD14(+)CD16(++)). The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-ß was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R) between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

Impaired lymphocyte profile in schistosomiasis patients with periportal fibrosis.

The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4(+)CD28(+) T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4(+) T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8(+) T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8(+) T cells, CD4(+)CD25(high) T cells, and CD4(+)CTLA-4(+) T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4(+)CD25(low) cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

Cytokine and Chemokine Profile in Individuals with Different Degrees of Periportal Fibrosis due to Schistosoma mansoni Infection.

Periportal fibrosis in schistosomiasis has been associated to the host immune response to parasite antigens. We evaluated the immune response in S. mansoni infected individuals with different degrees of periportal fibrosis. Cytokine and chemokines were measured in serum and in supernatants of PBMC cultures stimulated with the soluble adult worm (SWAP) or egg (SEA) antigens, using a sandwich ELISA. The levels of IL-5 in response to SEA were higher in individuals with moderate to severe fibrosis (310.9 pg/mL) compared to individuals without fibrosis (36.8 pg/mL; P = 0.0418). There was also a higher production of TNF-α in cultures stimulated with SWAP in patients with insipient fibrosis (1446 pg/mL) compared to those without fibrosis (756.1 pg/mL; P = 0.0319). The serum levels of IL-13 and MIP-1α were higher in subjects without fibrosis than in those with moderate to severe fibrosis. However a positive association between serum levels of IL-13, TNF-α, MIP-1α, and RANTES and S. mansoni parasite burden was found. From these data we conclude that IL-5 and TNF-α may participate in liver pathology in schistosomiasis. The positive association between IL-13, TNF-α, MIP-1α, and RANTES with parasite burden, however, might predict the development of liver pathology.