Systemic Cytokine and Chemokine Profiles in Individuals With Schistosoma mansoni Infection and Low Parasite Burden

Abstract

Intestinal schistosomiasis, caused by the parasitic trematode Schistosoma mansoni, is a chronic disease and the prolonged and continuous exposure to S. mansoni antigens results in a deviation of the host's immune response. For diagnosis, the Kato-Katz (KK) method is recommended, however, this method showed low accuracy in areas of low endemicity. This study aimed to characterize the cytokine and chemokine profile of individuals with an extremely low parasite load (<4 eggs per gram of feces), e.g., individuals who were detected by alternative parasitological methods, such as the saline gradient and/or Helmintex®. In order to search for immunological markers for infection, the immunological profile in serum samples of these individuals was then compared with patients detected with the KK method and with a higher parasite load and with individuals repetitively negative by extensive stool exams. The study was conducted in Northern Minas Gerais in a rural area of the Municipality of Januária. Serum samples of a total of 139 parasitologically well-characterized individuals were assessed for the following immunological markers by commercially available immunoassays: TNF-α, IL-1β, IL-6, IL-17A, IL-5, IL-10, IL-13, IL-33, IL-27, CCL3, CCL5, CXCL10, CCL11, and CCL17. As a result, there were no significant differences in concentrations or frequencies for immunological markers between egg-negative individuals or individuals with ultra-low (<4 epg) or low (4–99 epg) parasite loads. However, we found significant correlations between egg counts and eosinophil counts and between egg counts and IL-1β or TNF-α concentrations. The most striking alterations were found in individuals with the highest parasite load (≥100 epg). They had significantly higher TNF-α concentrations in serum when compared with individuals with a low parasite load (4–99 epg) and CCL17 concentrations were significantly elevated when compared with egg-negative individuals. Radar diagrams of frequencies for cytokine and chemokine responders in each infection group confirmed a distinct profile only in the infection group with highest parasite loads (≥100 epg).

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

“…However, the cytokine expression profile of PBMCs following PZQ therapy shows a mixed Th1/Th2/Th17 response with nearly all of the cytokines measured were upregulated compared to the cytokine profile at week 13 with the exceptions of TGFβ being downregulated and TNF-α and IL-6 showing no significant change. Destruction of the adult schistosome worm releases antigens that may be concealed from the host immune response, such as antigens in the tegument, thus causing a strong cellular immune response, although marked variability of cytokine expression between individuals can exist (Joseph et al, 2004a;Martins-Leite et al, 2008;Castro et al, 2018; Supplementary Figure 3).…”

Schistosoma mansoni infection is associated with decreased risk of respiratory allergy symptoms and low production of CCL2

“…However, the broad stimulus of the mitogen may recover the cellular memory immune response generated during the larval (acute) and egg (chronic) deposition phases. The production of type 1 cytokines, TNF-a, IL-6, IFN-c, with or without IL-10, by whole blood or mononuclear cells, has been reported in loads parasites above 100 epg faeces, present in the acute phase [27,[46][47][48], whereas, the IL-10 is marker of the Th2/Treg profile induced by soluble antigens of S. mansoni eggs [49,50]. In addition to IL-10, infection by S. mansoni induces regulatory factors such as Tregs cells, TGF-b and CTLA-4 in the modulation of the inflammatory response in allergy [2,51].…”

“…The airway epithelial cells of children with a history of wheezing demonstrate reduced CCL5, CCL2 and IL-6 [26]. Recently, it was reported that, in the context of infection with S. mansoni with or without allergic reactivity (anti-allergen IgE in serum), there was no difference in the levels of the chemokines CCL3, CCL5, CXCL10 or CCL11 [27,28]; however, there was an increase in plasma CXCL8 levels during acute S. mansoni infection [29]. These studies showed no correlation with allergy symptoms.…”

Previous History of American Tegumentary Leishmaniasis Alters Susceptibility and Immune Response Against Schistosoma mansoni Infection in Humans

“…The association of CCL17 and eosinophilia with S. mansoni infection was not unexpected, since these mediators are markers of a type-2 immune response, which is frequently reported in helminth-infected individuals ( 15 , 16 ). Activated eosinophils are an important source of IL-4, IL-5, and IL-13 ( 62 , 63 ), and this environment induces the production of CCL17 ( 64 ), which is described as a signature chemokine of helminth infection, especially S. mansoni , in humans ( 49 , 65 ). Moreover, Jakubzick et al ( 66 ) demonstrated that CCL17 production participates in CCR4 + -cell recruitment to S. mansoni -induced lung granulomas, stimulating Th2 inflammatory markers, and increasing the hydroxyproline content in the tissue.…”

“…Blood samples were collected in the morning after fasting and using EDTA-containing tubes for a complete blood count performed by a commercial local laboratory and EDTA-free tubes to obtain the serum for immunological analysis, as previously detailed ( 41 , 49 ). In the current work, data on hemoglobin levels and the number of circulating red blood cells, eosinophils, and platelets were evaluated as the median value and as frequency of altered values among individuals with different infection status.…”