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*‡

 

1 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.

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

4 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.

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

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

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

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

9 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.

Published by

Science Advances