Maternal Schistosomiasis: Immunomodulatory Effects With Lasting Impact on Allergy and Vaccine Responses

Abstract

Early exposure to immune stimuli, including maternal infection during the perinatal period, is increasingly recognized to affect immune predisposition during later life. This includes exposure to not only viral and bacterial infection but also parasitic helminths which remain widespread. Noted effects of helminth infection, including altered incidence of atopic inflammation and vaccine responsiveness, support further research into the impact these infections have for skewing immune responses. At the same time, despite a sea of recommendations, clear phenotypic and mechanistic understandings of how environmental perturbations in pregnancy and nursing modify immune predisposition and allergy in offspring remain unrefined. Schistosomes, as strong inducers of type 2 immunity embedded in a rich network of regulatory processes, possess strong abilities to shift inflammatory and allergic diseases in infected hosts, for example by generating feedback loops that impair T cell responses to heterologous antigens. Based on the current literature on schistosomiasis, we explore in this review how maternal schistosome infection could drive changes in immune system development of offspring and how this may lead to identifying factors involved in altering responses to vaccination as well as manifestations of immune disorders including allergy.

Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country

“…In utero exposure to helminths and other environmental factors has recently been shown to alter placental gene expression 36 and to influence the offspring’s propensity to develop allergies later in life 14,15 . Previous investigations of gene expression within the placental tissue have rarely considered potential expression differences between the fetal and maternal side of the placenta or possible differences in environmental exposure 37,38 .…”

“…Recent research indicates that early exposure to such a modified environment during gestation already primes the fetal immune system in utero and leads to enhanced immunological maturity at birth 14 . Indeed, it was recently demonstrated, that experimental chronic infection with the helminth Schistosoma mansoni during pregnancy influences the outcome of allergic asthma in offspring 15 .…”

Maternalschistosomiasisimpairs offspring IL-4 production and B cell expansion

“…Bolstering this is the finding that there is a significant reduction in IL-4 competent (GFP + ) CD4 T cells in the peripheral blood of these mice. This evidence suggests that prenatal helminth sensitization has a lasting effect on offspring immunity, and that offspring from mothers that were infected during pregnancy could be at a higher risk of infection with various pathogens due to a defect in homeostatic immunity as has been previously postulated [33], which will be the focus of future studies in our lab.…”

Prevalence of schistosomiasis and its association with anemia among pregnant women: a systematic review and meta-analysis

“…Other effects of schistosomiasis on pregnancy outcomes, such as reduced maternal-to-infant antibody transfer [ 50 , 55 ], infertility, preterm deliveries, and lower birth weights [ 9 ], need to be addressed. The adverse effects of schistosomiasis during pregnancy could be explained by the modulation of the immune response (change from Th1 toward Th2), which could be accompanied by immune modulation in newborns [ 3 , 4 ].…”

“…It was estimated that, in 2014, 40 million women of reproductive age had schistosomiasis ( Schistosoma haematobium, S. japonicum , and/or S. mansoni ) [ 2 ] . During pregnancy, helminth infections, including schistosomiasis, can lead to modulation of the immune response (change from Th1 toward Th2), increasing the susceptibility of pregnant women to various infections, such as influenza, malaria, measles, and toxoplasmosis, and their severity and can further lead to immune modulation in newborns [ 3 , 4 ]. Previous studies have reported that schistosomiasis in pregnancy is associated with anemia [ 5 – 7 ].…”