Altered Offspring Immunity in Maternal Parasitic Infections

Abstract

Maternal infection during pregnancy is known to alter the development and function of offspring’s immune system, leading to inappropriate immune responses to common childhood infections and immunizations. Although this is an expanding field, maternal parasitic infections remain understudied. Millions of women of reproductive age are currently at risk for parasitic infection, whereas many pregnant, chronically infected women are excluded from mass drug administration due partially to a lack of resources, as well as fear of unknown adverse fetal developmental outcomes. In areas endemic for multiple parasitic infections, such as sub-Saharan Africa, there are increased rates of morbidity and mortality for various infections during early childhood in comparison with nonendemic areas. Despite evidence supporting similar immunomodulatory effects between various parasite species, there is no clear mechanistic understanding of how maternal infection reprograms offspring immunity. This brief review will compare the effects of selected maternal parasitic infections on offspring immunity.

Maternal infection causes dysfunctional BCR signaling in male offspring due to aberrant Xist expression

“…Although it is well established that maternal infections, specifically parasitic ones, can shape offspring immunity (10)(11)(12)(13)(60)(61)(62)(63), it is still unknown what factors influence offspring B cell development. Many current studies focus on TORCH (Toxoplasmosis, other (syphilis, varicellazoster, parvovirus B19), Rubella, Cytomegalovirus, and Herpes) infections (64), or common congenital infections, with little effort on how non-congenital maternal infections affect offspring immunity.…”

“…While an inappropriate excess of Th2 cytokines can prolong virus clearance (7), these cytokines can also decrease chronic, autoimmune-induced inflammation (8). Maternal parasitic infections can mirror these disease outcomes in offspring, such as decreased responsiveness to antigens and protection from the development of some allergies and other chronic diseases (9)(10)(11)(12). Yet, a decrease in Th2 cytokines is observed in mouse models of maternal schistosomiasis, due to epigenetic regulation of the transcription of these cytokines (10,13).…”

Impact of helminth–microbiome interactions on childhood health and development—A clinical perspective

“…For example, although helminths cannot pass the placental barrier, children born to mothers infected with either Brugia malayi or soil‐transmitted helminths are more susceptible to future helminthiasis due to their immune systems being primed for infection in utero 59,60 . In general, immune hyporesponsiveness leads to an increased susceptibility to other kinds of infections, such as tuberculosis and HIV 8,9,58 . Furthermore, helminth infection during pregnancy has been linked to a decreased efficacy of childhood vaccinations later in life, which correlates with the decreased response to common vaccines observed in certain communities with a high prevalence of parasitic infections 9,61–63 .…”

“…In general, immune hyporesponsiveness leads to an increased susceptibility to other kinds of infections, such as tuberculosis and HIV 8,9,58 . Furthermore, helminth infection during pregnancy has been linked to a decreased efficacy of childhood vaccinations later in life, which correlates with the decreased response to common vaccines observed in certain communities with a high prevalence of parasitic infections 9,61–63 . These studies have indicated that either pre‐ or post‐natal exposure to helminths can have a long‐lasting effect on the development and responsiveness of the child's immune system to environmental stimuli.…”

“…In children, heavy Ascaris burden peaks at 24–30 months of life, correlating with the time that children gain more mobility, independence, and thus come into greater contact with their environment 4 . During pregnancy, the hormonal and immunological changes that women's bodies undergo to protect their developing fetus also results in a permissive environment for parasitic infection, translating into an increased risk of malnutrition, reduced birth weight, infant mortality, impaired development and the prevalence of various chronic diseases later in life 2,5–9 . Despite the recognized global burden of parasitic worm infection, millennia of co‐evolution between helminths and their human hosts have led to the emergence of the ‘hygiene hypothesis’, postulating the existence of other, protective effects that can be exerted on humans by helminths, which have been lost in Westernized countries and urban communities along with the eradication of these parasites 10 .…”