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PLoS One. 2014 Jan 23;9(1):e84763. doi: 10.1371/journal.pone.0084763. eCollection 2014.

Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection.

Author information

1
Department of Medicine and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
2
Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC, United States of America ; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
3
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
4
Vrije Universiteit, VUMC, Department of Molecular Cell Biology, Amsterdam, The Netherlands.
5
Translational Research Center for Gastrointestinal Disorders, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.
6
United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, & Immunology Laboratory, Beltsville, Maryland, United States of America.

Abstract

Parasitic enteric nematodes induce a type 2 immune response characterized by increased production of Th2 cytokines, IL-4 and IL-13, and recruitment of alternatively activated macrophages (M2) to the site of infection. Nematode infection is associated with changes in epithelial permeability and inhibition of sodium-linked glucose absorption, but the role of M2 in these effects is unknown. Clodronate-containing liposomes were administered prior to and during nematode infection to deplete macrophages and prevent the development of M2 in response to infection with Nippostrongylus brasiliensis. The inhibition of epithelial glucose absorption that is associated with nematode infection involved a macrophage-dependent reduction in SGLT1 activity, with no change in receptor expression, and a macrophage-independent down-regulation of GLUT2 expression. The reduced transport of glucose into the enterocyte is compensated partially by an up-regulation of the constitutive GLUT1 transporter consistent with stress-induced activation of HIF-1α. Thus, nematode infection results in a "lean" epithelial phenotype that features decreased SGLT1 activity, decreased expression of GLUT2 and an emergent dependence on GLUT1 for glucose uptake into the enterocyte. Macrophages do not play a role in enteric nematode infection-induced changes in epithelial barrier function. There is a greater contribution, however, of paracellular absorption of glucose to supply the energy demands of host resistance. These data provide further evidence of the ability of macrophages to alter glucose metabolism of neighboring cells.

PMID:
24465430
PMCID:
PMC3900397
DOI:
10.1371/journal.pone.0084763
[Indexed for MEDLINE]
Free PMC Article
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