Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

Mais um artigo bem interessante seguindo a onda dos estudos envolvendo a importância da microbiota para a resposta imune:

Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

Hachung Chung, Sunje J. Pamp, Jonathan A. Hill, Neeraj K. Surana, Sanna M. Edelman, Erin B. Troy, Nicola C. Reading, Eduardo J. Villablanca, Sen Wang, Jorge R. Mora, Yoshinori Umesaki, Diane Mathis, Christophe Benoist, David A. Relman, and Dennis L. Kasper

Cell, Volume 149, Issue 7, 1578-1593, 22 June 2012

Highlights

- Mouse and human microbiota differ in bacterial species, primarily within Firmicutes

- Human microbiota (HMb) colonized mice have a global immunodeficiency like GF mice

- HMb induced less T cell proliferation and activation than mouse microbiota (MMb)

- HMb mice are more susceptible to enteric and disseminated infection than MMb mice

Summary

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4⁺ and CD8⁺ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression—all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.

An Overview of the Regulation of the Mouse Small Intestinal Immune System by MMb versus HMb, Related to Table S3 Microbiota: In both MMb and HMb mice, Bacteroidetes were the most dominant phyla followed by Firmicutes, and Proteobacteria in the gut. Within the Bac- teroidetes phyla, 34% of OTU (or bacterial species) were shared by both MMb and HMb. Among the OTUs within the Firmicutes, only 1.5% were shared by both MMb and HMb. SFB - a commensal bacterium and member of the Firmicutes - was detected in MMb, but not HMb - exemplifying host specificity within the Firmicutes phyla. PP, MLN: Compared to MMb mice, HMb mice PP/MLN contains lower absolute numbers of DCs and T cells. The lower rate of T cell proliferation observed in HMb mice could contribute to the lower absolute number of small intestinal T cells in HMb mice. In both MMb and HMb mice, proliferating T cells in PP/MLN upregulate the intestinal homing receptors a4b7 and CCR9. LP: Proliferating T cells in the PP/MLN empty into the thoracic duct, enter the blood stream, and exit into the gut mucosa through intestinal venules in the small intestinal LP where MAdCAM and CCL25—ligands of a4b7 and CCR9, respectively—are expressed. No differences were observed in the expression of MAdCAM and CCL25 between MMb and HMb mice. Due to low numbers of proliferating T cells originating from the HMb mice PP/MLN, the HMb mice small intestinal LP have lower numbers of T cells compared to MMb mice LP. A lower number of secretory IgA+ cells were observed in the LP of HMb mice compared to the same compartment in MMb mice. Epithelium: Low number of T cells in the small intestinal LP of HMb mice can lead to lower numbers of IELs embedded in the HMb mice epithelium, compared to the MMb epithelium. MMb mice epithelial cells, but not HMb epithelial cells, upregulate RegIIIg an antimicrobial peptide. The expression of chemokines CCL20, CCL28, and CXCL9 are induced by MMb, but not HMb.