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

Matthew G. Darby,Alisha Chetty,Dunja Mrjden,Marion Rolot,K. Smith,Claire Mackowiak,D. Sedda,D. Nyangahu,H. Jaspan,K. Toellner,A. Waisman,V. Quesniaux,B. Ryffel,A. Cunningham,B. Dewals,F. Brombacher,W. Horsnell

Published 2019 in Science Advances

ABSTRACT

Mothers transfer immune cells via breastfeeding to provide offspring with long-term protection from parasitic infection. 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.

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