Bacteria associated with immunoregulatory cells in mice

Abstract

This study examined bacteria-immune interactions in a mouse model possessing microbiota-dependent immune regulatory features similar to those occurring in human atopy, colitis, and immune regulation. Associations between the abundance of several bacterial phylotypes and immunoregulatory target cell types were identified, suggesting that they may play a role in these phenotypes.

FIG. 1.

Bacterial community profiles of various intestinal regions and compartments from CF and RF mice. Profiles were obtained by RISA. For each mouse type-intestinal region combination, bacterial communities from two different mice are shown. Arrow indicates a 1-kb DNA ladder (Invitrogen) (top band = 1,018 bp; bottom band = 298 bp). Sm, small.

FIG. 2.

Associations between the amounts of the bacterial phylotypes and MZ B and iNK T cells in CF and RF mice. Phylotypes were measured in several intestinal regions and compartments by using sequence-selective qPCR assays (see Table S1 in the supplemental material for more information on the phylotypes). Lymphocytes were measured by flow cytometry (a = %MZ B cells [CD21 + IgM^hi] in spleen, b = %MZ B cells [CD21 + IgD] in spleen, c = NK1.1 + % in liver, and d = CD1d tetramer + % in liver). Phylotypes whose abundance correlated (P < 0.05) with lymphocyte levels are shown as colored blocks. The strengths of the trends (Pearson's correlation coefficients) are depicted by the brightness of the colors (see scale bar). n = 8 for the luminal and mucosal compartments of the small intestine and the luminal compartment of the colon, and n = 4 for the mucosal compartment of the colon. The right side of the figure shows phylotypes that increased (black and white checkered boxes) in RF mice treated with CD8 and NK1.1 antibodies (RF-CD8-A) or RF mice with a CD8⁺ T-cell knockout (RF-CD8-KO) compared to RF mice; these results are from the experiments depicted in Fig. 3 and are presented here to facilitate interpretation of all three sets of experiments.

FIG. 3.

Bacterial phylotypes whose population densities changed after reducing or abolishing CD8⁺ T-cell populations in RF mice. Left column, CD8-NK1.1 antibody-treated RF mice (RF-CD8-A) compared to RF mice (P < 0.05). Right column, RF mice containing a CD8 knockout (RF-CD8-KO) compared to RF mice (P < 0.05). Phylotypes were measured by sequence-selective qPCR. n = 4 to 6 for RF-CD8-A mice and 2 to 4 for RF mice and RF-CD8-KO mice. Columns show means and standard errors.