Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring

Abstract

Maternal immune transfer is the most significant source of protection from early-life infection, but whether maternal transfer of immunity by nursing permanently alters offspring immunity is poorly understood. Here, we identify maternal immune imprinting of offspring nursed by mothers who had a pre-conception helminth infection. Nursing of pups by helminth-exposed mothers transferred protective cellular immunity to these offspring against helminth infection. Enhanced control of infection was not dependent on maternal antibody. Protection associated with systemic development of protective type 2 immunity in T helper 2 (TH2) impaired IL-4Rα−/− offspring. This maternally acquired immunity was maintained into maturity and required transfer (via nursing) to the offspring of maternally derived TH2-competent CD4 T cells. Our data therefore reveal that maternal exposure to a globally prevalent source of infection before pregnancy provides long-term nursing-acquired immune benefits to offspring mediated by maternally derived pathogen-experienced lymphocytes.

Impact of Helminth Infections on Female Reproductive Health and Associated Diseases

“…In addition to modulation of allergies and autoimmunity, Darby et al (72) recently demonstrated how pre-conception maternal helminth exposure influences offspring immunity to helminth infection. Prior murine hookworm, Nippostrongylus brasiliensis infection imprinted Th2 immunity in female mice, which was transferred via breast milk and conferred protection against the parasite in their offspring.…”

Maternalschistosomiasisimpairs offspring IL-4 production and B cell expansion

“…In this study we report the generation of a maternal Schistosoma mansoni infection model in dual IL-4 reporter mice. Our results indicate that in utero egg antigen sensitization occurs, which is consistent to what has been published by other authors [24] and confers a state of immune-hyporesponsiveness in the offspring at steady state, this study does not differentiate between trans-placental antigen exposure and sensitization through breastfeeding; however, it has been previously suggested that exposure to parasitic antigens, either in utero or via breast milk, diminishes the heterologous response [24], and in some other cases nursing by infected mothers protected offspring against infection with the same helminth [25]. We observed anti- S. mansoni egg antigen-specific IgG1 (the dominant isotype produced against egg antigens [16]) at 35, 90 and 180 days of age in mice from infected mothers and no detectable titers in mice born to uninfected controls, suggesting either maternal antibody, antibody-secreting cell transfer to the offspring, or in situ antibody production by the offspring.…”

Siamon Gordon: A half-century fascination with macrophages

“…A further example of maternal-neonatal transfer of macrophages (Darby et al, 2019) demonstrated that preconception helminth infection can transfer cellular immunity to offspring via nursing through T cells rather than IgA. Since milk is a rich source of macrophages, it is plausible that macrophages surviving the acid environment of the stomach can enter the infant body through an immature or leaky intestine.…”