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.
