Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 310, Issue 10, Pages G822-G831Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00440.2015
Keywords
microbiota; innate immunity; intestinal homeostasis
Categories
Funding
- Canadian Institutes for Health Research (CIHR)/Canadian Digestive Health Foundation (CDHF)
- Alberta Innovates-Health Solutions (AI-HS)
- CIHR/Canadian Association of Gastroenterology (CAG)/Janssen
- AI-HS post-doctoral fellows awards
- Canada Research Chair (CRC) (Tier 1) in Intestinal Immunophysiology
- Crohn's Colitis Canada
- Queen Elizabeth II Graduate Scholarship
Ask authors/readers for more resources
Fernando MR, Saxena A, Reyes JL, McKay DM. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages. Am J Physiol Gastrointest Liver Physiol 310: G822-G831, 2016. First published March 24, 2016; doi:10.1152/ajpgi.00440.2015.-The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4) s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4) s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4) s and M(IL-4 + butyrate) s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4) s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available