Lactobacillus brevis KB290 With Vitamin A Ameliorates Murine Intestinal Inflammation Associated With the Increase of CD11c+ Macrophage/CD103- Dendritic Cell Ratio

Abstract

Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal inflammation. Little is known about how the ratio is regulated by lactic acid bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of LAB/Bif to this ratio.

Methods: We established an in vitro experimental system using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective LAB/Bif strains. The selected strain's effect on the colonic CD11c+ MP/CD103- DC ratio and intestinal inflammation was examined in mice, and the strain's underlying mechanisms were investigated in vitro.

Results: We screened 19 strains of LAB/Bif, and found that Lactobacillus brevis KB290 (KB290) increased the CD11c+ MPL/CD103- DCL cell ratio only in the presence of a vitamin A (VA) metabolite, retinoic acid (RA). Supplementation of KB290 with VA increased the CD11c+ MP/CD103- DC ratio in healthy mouse and prevented the disruption of the ratio during colitis. Supplementation of KB290 with pro-VA (β-carotene) also increased the ratio in healthy mouse and ameliorated the development of colitis. The ratio was increased by reduction of CD103- DCs (or CD103- DCL cells). Our in vitro data suggested that KB290 induced cell death in CD103- DCL cells in the presence of RA signaling.

Conclusions: Supplementation of KB290 with VA increases the colonic CD11c+ MP/CD103- DC ratio associated with the amelioration of murine colitis, suggesting a possible way to control intestinal inflammation by LAB.

Keywords: CD103− dendritic cells; CD11c+ macrophages; Lactobacillus brevis KB290; bifidobacteria; intestinal inflammation; lactic acid bacteria; vitamin A.