The Human Milk Oligosaccharide 2′-Fucosyllactose Quenches Campylobacter jejuni–Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa123
| Autor: | Yu, Zhuo-Teng, Nanthakumar, N Nanda, Newburg, David S |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Inflammation
Male Nutrition and Disease Milk Human Tumor Necrosis Factor-alpha Chemokine CXCL2 Interleukin-1beta Interleukin-8 Epithelial Cells Gastrointestinal Microbiome Campylobacter jejuni Mice Inbred C57BL Disease Models Animal Mice Cell Line Tumor Campylobacter Infections Animals Humans RNA Messenger Intestinal Mucosa HT29 Cells Trisaccharides |
| Popis: | Campylobacter jejuni causes diarrhea worldwide; young children are most susceptible. Binding of virulent C. jejuni to the intestinal mucosa is inhibited ex vivo by αThe simplest αHuman epithelial cells HEp-2 and HT-29 infected with the virulent C. jejuni strain 81-176 human isolate were treated with 5 g 2'-FL/L, and the degree of infection and inflammatory response was measured. Four-week-old male wild-type C57BL/6 mice were fed antibiotics to reduce their intestinal microbiota and were inoculated with C. jejuni strain 81-176. The sensitivity of the resulting acute transient enteric infection and immune response to inhibition by 2'-FL ingestion was tested.In HEp-2 and HT-29 cells, 2'-FL attenuated 80% of C. jejuni invasion (P0.05) and suppressed the release of mucosal proinflammatory signals of interleukin (IL) 8 by 60-70%, IL-1β by 80-90%, and the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2) by 50% (P0.05). Ingestion of 2'-FL by mice reduced C. jejuni colonization by 80%, weight loss by 5%, histologic features of intestinal inflammation by 50-70%, and induction of inflammatory signaling molecules of the acute-phase mucosal immune response by 50-60% (P0.05). This acute model did not induce IL-17 (adaptive T cell response), a chronic response.In human cells in vitro (HEp-2, HT-29) and in a mouse infection model that recapitulated key pathologic features of C. jejuni clinical disease, 2'-FL inhibited pathogenesis and its sequelae. These data strongly support the hypothesis that 2'-FL represents a new class of oral agent for prevention, and potentially for treatment, of specific enteric infectious diseases. |
| Databáze: | OpenAIRE |
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