Premium
CX3CR1 deficiency alters response to L. reuteri treatment of DSS‐induced colitis in mice (902.10)
Author(s) -
Ahl David,
Roos Stefan,
Phillipson Mia,
Holm Lena
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.902.10
Subject(s) - lactobacillus reuteri , cx3cr1 , colitis , proinflammatory cytokine , chemokine , immunology , chemistry , medicine , probiotic , immune system , microbiology and biotechnology , inflammation , biology , chemokine receptor , bacteria , genetics
Preliminary results from our laboratory suggest that two strains of the probiotic bacteria Lactobacillus reuteri ameliorate DSS‐induced colitis in mice. The chemokine receptor CX3CR1 is expressed by circulating monocytes and by intestinal lamina propria resident cells believed to be macrophages and/or dendritic cells. Mice deficient in CX3CR1 (CX3CR1GFP/GFP) develop an aggravated DSS‐induced colitis, suggesting a role of CX3CR1 in the maintenance of colonic homeostasis. The aim of the study was to investigate if the protective mechanism of L. reuteri R2LC or ATCC PTA 4659 on DSS‐induced colitis involve CX3CR1. Colitis was induced by 3% DSS in drinking water, administrated for 8 days to C57Bl/6 (wt) and CX3CR1GFP/GFP mice. Some of the mice were given L. reuteri R2LC or ATCC PTA 4659 by gavage once daily for 15 days in addition to DSS for the last 8 days. Disease activity index (DAI) was calculated from clinical symptoms and measurements of the pro‐inflammatory cytokines IL1‐β, IL‐6, TNF‐α and mKC were also performed in colonic tissue samples. Immunohistochemical (IHC) staining of colonic tissue sections was used to characterize the population of macrophages and dendritic cells. In the CX3CR1GFP/GFP mice, DAI increased slightly more by DSS than in the wt, and the L. reuteri strains did not significantly reduce DAI, in contrast to significant reductions in wt mice. The levels of all proinflammatory cytokines were significantly higher in DSS treated CX3CR1GFP/GFP mice than in wt. Treatment with L. reuteri significantly reduced most cytokines in wt and CX3CR1GFP/GFP mice. Preliminary data from IHC stainings show a phenotypically skewed population of lamina propria immune cells in CX3CR1GFP/GFP mice. These results indicate that the protective role of the two different strains of L. reuteri on DSS‐induced colitis is slightly reduced in CX3CR1GFP/GFP mice, compared to wt mice. Thus, the mechanism by which L.reuteri bacterial strains ameliorate colitis might involve CX3CR1.