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

Darby et al., Sci. Adv. 2019; 5 : eaav3058

Matthew G. Darby1*, Alisha Chetty1*, Dunja Mrjden1†, Marion Rolot2, Katherine Smith1,3, , Claire Mackowiak4, Delphine Sedda4, Donald Nyangahu1, Heather Jaspan1,5, Kai-Michael Toellner6, Ari Waisman7, Valerie Quesniaux4, Bernhard Ryffel4, Adam F. Cunningham6,8*, Benjamin G. Dewals2*, Frank Brombacher1,9,10‡, William G. C. Horsnell1,8,4*‡

 

Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town 7925, South Africa.

2 Fundamental and Applied Research in Animals and Health (FARAH), Immunology-Vaccinology, Faculty of Veterinary Medicine (B43b), University of Liège, Liège, Belgium.

Institute of Infection and Immunity, University of Cardiff, Cardiff, UK.

Laboratory of Molecular and Experimental Immunology and Neuro-genetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, 45000 Orléans, France.

Seattle Children’s Research Institute and Departments of Paediatrics and Global Health, University of Washington, Seattle, WA, USA.

Institute of Immunology and Immunotherapy and School of Immunity and Infection, University of Birmingham, B15 2TT Birmingham, UK.

Institute for Molecular Medicine, University of Mainz, Mainz, Germany.

Institute of Microbiology and Infection, University of Birmingham, B15 2TT Birmingham, UK.

International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.

10 South African Medical Research Council, Cape Town, South Africa.

*These authors contributed equally to this work.

†Present address: Department of Pathology, Stanford Blood Center, Stanford University, 3373 Hillview Ave., Palo Alto, CA 94304, USA.

‡Corresponding author. Email: wghorsnell@gmail.com (W.G.C.H.); brombacherfrank@gmail.com (F.B.)

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-4R−/− 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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