Recent publication: Gut Microbiota and the Neonatal Immune system

At birth, when neonate meets for the first time its external environment, the immune system is dominated by anti-inflammatory responses. This phenomenon called « neonatal tolerance », long described as being due to the immaturity of the immune system, is actually crucial to avoid the development of excessive and deleterious responses that can be harmful. However, neonates are also facing a lot of dangerous pathogens he has to fight. Therefore, induction of immune protection is as well essential in early life. The maintenance of this dynamic balance between tolerance and protection is a fundamental feature of the immunity of neonates who overall are more susceptible to infections and develop poor vaccine responses.
Previously, the team of Pr. Véronique Flamand (Institute for Medical Immunology) has described a population of precursors of cDC1 (called pre-cDC1), that is the dominant splenic cDCs population during the first week of life and that displays unique regulatory properties. Indeed, able to produce IL-12p40 and IL-10 depending on the environment, pre-cDC1 are directly involved in the orchestration of neonatal immune responses and in the protection against Listeria monocytogenes infection through the induction of CD8+ T-cell responses.
In this recent work published in Gut, Arnaud Köhler and colleagues show that spontaneous functional maturation of pre-cDC1 in the spleen is dependent on neonatal gut microbiota colonization that happens directly after birth. From a mechanistic point of view, this microbiota-effect relies on the production of TNF by innate myeloid cells that directly targets pre-cDC1 population to kick-start its maturation while reducing its regulatory profile.

Original article: Köhler A, Delbauve S, Smout J, Torres D and Flamand V. “Very early-life exposure to microbiota-induced TNF drives the maturation of neonatal pre-cDC1”. Gut 2020