Fetal immune development is directly modulated by maternal immune cells during pregnancy in mice

Introduction During mammalian pregnancy, maternal immune cells transfer from the mother to the fetus and are referred to as maternal microchimeric cells (MMc). Insights into the functional role of MMc are still unknown. To address this gap in knowledge, we developed a mouse model in which offspring are significantly devoid of MMc to investigate and aimed to test if MMc influence fetal immune development.

Methods We used two allogeneic mating strategies in order to generate offspring with physiological number of MMc as controls (MMc^pos) and with low number of MMc (MMc^low).Flow cytometry was employed to quantify MMc frequencies and to investigate the hematopoietic stem cell (HSC) and immune cell subsets in fetal bone marrow. HSCs transcriptome was sequenced to identify differentially expressed genes.

Results We identified a number of significantly differentially expressed genes among HSC in MMc^lowcompared to MMc^posoffspring, which coded for myeloid differentiation. Immune phenotyping of fetal bone marrow revealed a higher frequency of common myeloid precursors in MMc^posoffspring, along with a significantly increased frequency of monocytes. Restoring MMc levels in MMc^lowoffspring by adoptive transfer of immune cells significantly restored the frequency of monocytes in offspring. Differences of reproductive fitness, gene imprinting and microbiome between pregnancies yielding to MMc^lowor MMc^posoffspring – which could confound the findings on fetal immune development – were ruled out.

Conclusion We here provide evidence that MMc favor the differentiation of monocytes from fetal bone marrow-derived HSPC, which may yield to an enhanced immunity towards early life pathogen challenges.

Publication History

Article published online:
07 October 2020