Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

Abstract

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-β 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.

Elucidation of Cellular Responses in Non-human Primates With Chronic Schistosomiasis Followed by Praziquantel Treatment

“…This increase in the number of CD8 + T cells, together with the observed increase in IFN-γ may be a response to egg antigens during the chronic phase of schistosomiasis and has been hypothesized to be antifibrinogenic (Pancre et al, 1999;Henri et al, 2002). Furthermore, monocytes have been implicated in the immunopathogenesis of periportal fibrosis (Fernandes et al, 2014) and that intermediate CD14 ++ CD16 + monocytes have an enhanced ability to bind cercarial and egg excretory/secretory products which may affect an infected individual's ability to respond immunologically to infection (Turner et al, 2014). NK cells and NKT cells reverted back to naïve levels as the immune response shifted form innate immunity toward adaptive immunity.…”

Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease

“…Thus, it is important to define the monocyte subsets in parasitic infectious diseases with an inflammatory component. For instance, the intermediate and the classical monocytes are involved in the pathogenesis of both protozoa and helminth diseases, such as leishmaniasis, malaria, schistosomiasis, and filariasis (36–40). The goal of this study was to determine the monocyte subset percentages in peripheral blood and plasma cytokines levels in chagasic patients with different clinical stages.…”

“…Cytokines produced by monocytes including TNF-α and IL-6 and soluble CD14 are correlated with severe congestive heart failure (30–32); also soluble TNF receptor can be a predictor of mortality in the same condition (33, 34). Inflammatory monocytes (CD16+) have been associated with the pathogenesis of several infectious diseases including some caused by parasites (35–40). Currently, monocytes are phenotypically classified into three subsets according to the CD14 (bacterial LPS receptor) and CD16 (IgG low affinity receptor) expression: classical (CD14++ CD16–), intermediate (CD14++ CD16+), and non-classical monocytes (CD14+ CD16++) (41, 42).…”

Monocyte and Macrophage-Mediated Pathology and Protective Immunity During Schistosomiasis

“…Despite of their protective functions, monocytes also induce fibrosis (Fernandes et al, 2014). For example, B1 cells secrete IL-10 after S. japonicum infection and inhibit CCL2 chemokine (ligand CCR2) production, leading to reduced Ly6C high monocytes and fibrosis in the liver (Yong et al, 2019).…”

“…For example, B1 cells secrete IL-10 after S. japonicum infection and inhibit CCL2 chemokine (ligand CCR2) production, leading to reduced Ly6C high monocytes and fibrosis in the liver ( Yong et al, 2019 ). Moreover, CD14 high CD16 – and CD14 low/– CD16 high monocytes from schistosomiasis patients with liver fibrosis increase the expression of TGF-β ( Fernandes et al, 2014 ). In addition, stimulation of monocytes with soluble egg antigen (SEA) upregulates the expression of TGF-β ( Wolde et al, 2020 ; Figure 2 ).…”