Type 2 Immunity at the Interface Between Helminth Infection and Stunting

Abstract

Early life, defined as before the age of two, represents a critical development window. Many development-associated issues, like stunting, arise from suboptimal conditions during this period. Stunting, defined as two standard deviations below the height-for-age median, affects almost 30% of children under five. While many factors contribute to stunting, epidemiological evidence emphasizes that early life helminth infections, combined with undernutrition, may be major drivers. Helminths induce a potent type 2 immune response, which, potentially favoured in undernourished conditions, can modify systemic metabolism linked to development. Despite their prominence in developing countries, no publications have reported the early life interactions between helminths, undernutrition, and stunting. Thus, we seek to elucidate a potential relationship between these variables. We hypothesize that undernutrition increases the anti-helminth type 2 immune response, exacerbating early life stunting. Mouse pups are weaned onto an undernourished or control diet and are subsequently infected with a well-characterized helminth. Two- or four-weeks post-infection, immune cells and antibodies are quantified using various imaging and quantitative methods. Our lab has established a murine stunting phenotype reliant on both helminth infection and undernutrition, and our data suggest that a type 2 immune response may drive stunting. While mice are valuable models for studying this interaction, they possess temporal developmental differences from humans. Our preliminary data suggest that our stunting model depends on a type 2 immune response. This is the first study examining this response in an interplay between undernutrition, helminth infection, and stunting—an initial step towards addressing determinants of childhood stunting.