Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.

TitleRapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.
Publication TypeJournal Article
Year of Publication2014
AuthorsPickard, JM, Maurice, CF, Kinnebrew, MA, Abt, MC, Schenten, D, Golovkina, TV, Bogatyrev, SR, Ismagilov, RF, Pamer, EG, Turnbaugh, PJ, Chervonsky, AV
JournalNature
Volume514
Issue7524
Pagination638-41
Date Published2014 Oct 30
ISSN1476-4687
KeywordsAnimals, Anorexia, Bacteria, Citrobacter rodentium, Dendritic Cells, Disease, Eating, Epithelium, Fatty Acids, Female, Fucose, Fucosyltransferases, Gene Expression Regulation, Bacterial, Glycosylation, Immune Tolerance, Immunity, Innate, Interleukins, Intestine, Small, Ligands, Male, Metabolic Networks and Pathways, Mice, Microbiota, Protective Factors, Symbiosis, Toll-Like Receptors, Virulence Factors
Abstract

Systemic infection induces conserved physiological responses that include both resistance and 'tolerance of infection' mechanisms. Temporary anorexia associated with an infection is often beneficial, reallocating energy from food foraging towards resistance to infection or depriving pathogens of nutrients. However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin (IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress.

DOI10.1038/nature13823
Alternate JournalNature
PubMed ID25274297
PubMed Central IDPMC4214913
Grant ListAI42135 / AI / NIAID NIH HHS / United States
AI96706 / AI / NIAID NIH HHS / United States
DK42086 / DK / NIDDK NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P30 DK042086 / DK / NIDDK NIH HHS / United States
P50 GM068763 / GM / NIGMS NIH HHS / United States
R01 AI090084 / AI / NIAID NIH HHS / United States
R01 AI095706 / AI / NIAID NIH HHS / United States
T32 AI007090 / AI / NIAID NIH HHS / United States
T32 AI065382 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
UL1 TR000430 / TR / NCATS NIH HHS / United States