Maternal Microbiota Educates the Immune System of the Offspring Through Natural Antibodies

The impact of maternal microbiota during foetal life on the overall immune system development and health of the offspring is not clearly understood. We have found that reversible colonisation of pregnant germ free mice impacts on the development of innate immunity in the pups. The offspring from mothers exposed to intestinal microbes only during the pregnancy showed an increase in intestinal NKp46⁺Rorγt⁺ innate lymphoid cells and F4/80⁺CD11c⁺ mononuclear cells (iMNC). Local F4/80⁺CD11c⁺ iMNC differentiation was controlled by maternal microbiota. Moreover, the expression of genes involved in microbial adaptation was imprinted by maternal microbiota. The offspring from microbial treated mothers were protected against microbiota challenge preventing bacterial translocation to mesenteric lymph nodes and modulating gene expression. In the absence of natural antibodies and B cells, maternal microbiota failed to shape the innate immune system in the offspring resulting in increased bacterial translocation following challenge. Furthermore, maternal antibodies required loading with maternal bacterial products to control the development and the efficiency of the innate immune system of the offspring. Our results reveal the tremendous role played by maternal microbiota and natural antibodies in setting the baseline of the innate immune system in the offspring.

MGAT and SG, KDMc and AJM: these authors contributed equally to this work.