Immunity transmitted to the newborn through breast milk does not only pass through antibodies

In a study published in Science Advances, Benjamin G. DEWALS (ULiège) and William HORSNELL (University of Cape Town) found that long-term immunity against certain infections is also acquired during breastfeeding regardless of a transfer of maternal antibodies

Immune transfer from mother to child through breastfeeding is a very important source of protection against early infections. It is generally thought that this transfer of protection is limited to the period of breastfeeding, mediated by antibodies and lost when breastfeeding stops. In this study published in Science Advances and led by William Horsnell (University of Cape Town) in collaboration with Benjamin G. Dewals, F.R.S.-FNRS Research Associate at ULiège, the researchers show that this is not always the case: maternal exposure to a still highly prevalent infection, helminths (parasitic worms), is also found to provide offspring with long-term acquired immunity. Although the precise mechanisms have yet to be identified, they have been able to demonstrate that this immunity transfer could involve a transfer of immune cells during breastfeeding.

These surprising results, currently obtained on mouse models, provide insight into why some infections are better controlled in the long term when the presence of maternal antibodies has long since disappeared. In this way, they add a new dimension to the understanding of how the mother can influence the health of her offspring.

In mice, the researchers found that offspring breastfed by a mother infected with a parasitic worm before becoming pregnant had acquired immune protection against this infection. Unexpectedly, antibodies in breast milk were unable to transmit this protective effect to pups, while breast milk cells could be transmitted and associated with a long-term protective effect.

Indeed, mice born to uninfected mothers and adopted from birth by mothers previously infected with the parasite Nippostrongylus brasiliensis, have developed better immunity against the same parasite. Using transgenic mice unable to produce secreted antibodies, the researchers demonstrated that antibody transfer was not involved in the transfer of anti-parasite immunity. In contrast, in syngenetic conditions (where the progeny are histocompatible with the mother), immunity transfer was directly associated with the transfer of maternal cells, including Th2-type CD4+ T lymphocytes. In addition, mothers unable to produce a Th2 response in response to the parasite were also unable to transfer immunity to their offspring through breast milk. Finally, experiments in semi-allogenic conditions, i. e. mimicking natural conditions where the offspring share half of the histocompatibility molecules with their mother and father, have shown that immunity transfer also takes place.

The Immunology and Vaccinology Laboratory of FARAH (Fundamental and Applied Research for Animals and Health), at the Faculty of Veterinary Medicine of ULiège, is closely associated with this research. "We have been involved in the experimental implementation, interpretation and implementation phases of a number of experiments in my laboratory such as those involving the transfer of maternal immunity under semi-allogenetic conditions," explains Benjamin G. Dewals, head of the laboratory.

"In addition, the results presented in this publication form the basis of a thesis project initiated in 2018 to determine the immunity transfer mechanisms involved in conditions where maternal immune cells cannot theoretically be tolerated in the long term in offspring."

"We hope that this research will lead to human studies on how maternal exposure to pathogens before pregnancy can influence the health of the offspring. We are particularly interested in how these results can help design maternal immunization strategies that provide long-term protection for children," concludes William Horsnell, the study's lead author and latest author of the published article.

Reference

Pre-conception maternal helminth infection transfers via nursing long lasting cellular immunity against helminths to offspring, Science Advances, 29 May 2019, DOI: 10.1126/sciadv.aav3058

https://advances.sciencemag.org/content/5/5/eaav3058

Contact

Benjamin G. DEWALS,
F.R.S.-FNRS Qualified Researcher, Immunology and Vaccinology of FARAH (Fundamental and Applied Research for Animals and Health), at the Faculty of Veterinary Medicine of ULiège

Pictures

Illustration in the header : Microphotograph of a gravid female of the worm Nippostrongylus brasiliensis.
© Dr J.C. Hoving, University of Cape Town, South Africa

Ascaris lumbricoides worms in culture flasks expelled orally from a four year old girl at Red Cross Children’s Hospital, Cape Town, South Africa.
© Prof. W. Horsnell, Université de Cape Town

Team (left to right) : Justine JAVAUX, Françoise MYSTER, Benjamin G. Dewals, Marion Rolot