Neonatal microbial colonization in mice promotes prolonged dominance of CD11b(+)Gr-1(+) cells and accelerated establishment of the CD4(+) T cell population in the spleen.

Matilde B Kristensen,Hanne Frøkiær,Dina S M Damlund,Tine R Licht,Stine B Metzdorff,Anders Bergström,Lisbeth N Fink

doi:10.1002/iid3.70

Abstract

To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b+Gr-1+ splenocytes present perinatally was sustained for a longer period in conventionally colonized (CONV) mice than in mono-colonized (MC) and germfree (GF) mice, and the CD4+ T cell population established faster in CONV mice. At the day of birth, compared to GF mice, the expression of Cxcl2 was up-regulated and Arg1 down-regulated in livers of CONV mice. This coincided with lower abundance of polylobed cells in the liver of CONV mice. An earlier peak in the expression of the genes Tjp1, Cdh1, and JamA in intestinal epithelial cells of CONV mice indicated an accelerated closure of the epithelial barrier. In conclusion, we have identified an important microbiota-dependent neonatal hematopoietic event, which we suggest impacts the subsequent development of the T cell population in the murine spleen.

Highlights

During the past decades, the prevalence of allergies and autoimmune diseases has increased dramatically in the western world [1], and it is generally accepted that the microbial environment is a key player in the development of these disorders [2, 3]
We examined the development of cell subsets in the spleens of pups born by GF dams, Lactobacillus acidophilus NCFM mono-colonized (MC) dams, and CONV dams, and found that the establishment of the CD4þ T cell pool in the spleen was accelerated by conventional microbiota
In the period of 7–35 days after birth, the proportion of CD3þCD4þ T cells in spleens of all colonization groups increased from approximately 2% at postnatal day 7 (PND7) to 16–25% of the total splenocytes on PND35 (Fig. 1A)

Summary

Introduction

The prevalence of allergies and autoimmune diseases has increased dramatically in the western world [1], and it is generally accepted that the microbial environment is a key player in the development of these disorders [2, 3]. It is, still not clear how and when the intestinal microbiota influences the development of an immune system that is more prone to developing immune-related diseases as opposed to development of a healthy immune system. Maternal antibiotics use during pregnancy has been linked to an increased risk of early childhood asthma [6] These studies indicate that the microbiota in early life influences disease development. Events during perinatal life, affecting the first microbes that inhabit the epithelium at mucosal sites, may be determining for the ‘‘set-point’’ of the immune system

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