Modulation of Allergic Reactivity in Humans Is Dependent on Schistosoma mansoni Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum

Abstract

Helminth infections and allergies are characterized by a predominant type-2 immune response. In schistosomiasis, the Th-2 response is usually accompanied by induction of immunoregulatory mechanisms that contribute to worm survival and less severe schistosomiasis. Although helminth-induced immunomodulatory mechanisms seem to affect atopy, epidemiological studies on the relationship between helminths and allergy have been inconsistent, and data suggest that the modulatory effects may be influenced by helminth species, chronicity of infection, and parasite burden. Here we performed a cross-sectional study to investigate the effects of Schistosoma mansoni parasite burden and immune response on allergic reactivity of individuals living in a schistosomiasis endemic area in Brazil. Fecal samples from the participants were collected for extensive parasitological examinations by spontaneous sedimentation, Kato-Katz, Helmintex and Saline Gradient tests and molecular detection of S. mansoni by qPCR. Additionally, the concentrations of cytokines and chemokines, total IgE and IgE-reactivity to common house dust allergens were quantified from serum samples. IgE reactivity to dust allergens was detected in 47 individuals (23.8%), and 140 individuals (54.4%) were diagnosed with S. mansoni infection. Most of the infected population (108 individuals) presented very low parasite burden (≤12 eggs/g of feces). The frequency and intensity (p ≤ 0.03) of allergic reactivity were lower in S. mansoni-infected compared with non-infected individuals. Multivariable logistic regression models adjusted by age revealed that allergic reactivity was positively associated with low IL-10 response (OR, 4.55, 95% CI, 0.56–7.36) and high concentration of the inflammatory mediators IL-33 (OR, 2.70, 95% CI, 1.02–7.15) or TNF-α (OR, 6.88, 95% CI, 0.32–143.39) in serum, and inversely associated with S. mansoni infection (OR, 0.38, 95% CI, 0.16–0.87). Most importantly, the logistic regression demonstrated that the modulatory effects of Schistosoma infection depend on parasite burden, with individuals infected with ≤12 eggs/g of feces showing allergic IgE-reactivity similar to non-infected individuals Altogether, our data show that immunomodulation of allergic reactivity depends on S. mansoni burden, low type-2 inflammatory response, and high level of IL-10.

Negative Association of Interleukin-33 Plasma Levels and Schistosomiasis Infection in a Site of Polyparasitism in Rural Cameroon

“…A possible explanation of the observed low IL-33 plasma concentration in individuals chronically infected with S. mansoni , as is the case in our study, could be the early solicitation/utilization of this factor (IL-33). In fact, this line of thoughts gains support from a recent study that also reported low IL-33 blood levels in S. mansoni positive participants (41).…”

“…Another possible explanation for the reduced levels of plasma IL-33 in S. mansoni infected participants we observed could be the parasite-driven impairment of IL-33 production (41). Such a stratagem has recently been described for a parasitic nematode where a factor, HpARI (Alarmin release inhibitor) was identified and shown to tether IL-33 to necrotic cells preventing its release (61).…”

Functional Inhibition of Natural Killer Cells in a BALB/c Mouse Model of Liver Fibrosis Induced by Schistosoma japonicum Infection

“…Previous research showed that IL-10 reduced inflammation and promoted the repair process (Bodaan et al, 2016). Some reports showed that after being infected with S. mansoni, high levels of IL-10 could regulate the frequency and intensity of allergic reactivity (Resende et al, 2019). We concluded that at about 8 weeks post-infection, the mice were engaged in repairing the damage caused by inflammation.…”

The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications

“…A recent study has uncovered that patients infected with Schistosoma mansoni present with suppressed immune responses against dust mite allergen. This finding was further associated with increased IL-10, but an inverse correlation with IL-33 (Resende et al, 2018). While it is unrealistic to expect a patient to willingly harbor a helminthic infection to combat a chronic infection such as allergy, there are groups investigating the therapeutic potential of the helminth exosome.…”