Journal Article

Role of Macrophages in the Altered Epithelial Function during a Type 2 Immune Response Induced by Enteric Nematode Infection

Riera, Diana C, Palaniyar, Nades, Zhao, Aiping, Notari, Luigi, Shea-Donohue, Terez, Madden, Kathleen B, Vanuytsel, Tim, Bohl, Jennifer A, McLean, Leon P, van Rooijen, Nico, Sun, Rex, Urban, Joseph F

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Absorption / Animals / Biological Transport / Biology / Bisphosphonates / Cells, Cultured / Clodronic acid / Clodronic Acid - administration & dosage / Clodronic Acid - pharmacology / Cytokines / Down-regulation / energy / Enterocytes - immunology / Enterocytes - metabolism / Enterocytes - parasitology / Female / Gene Expression / Glucose / Glucose - metabolism / Glucose transport / Glucose transporter / Glucose Transporter Type 1 - genetics / Glucose Transporter Type 1 - metabolism / Glucose Transporter Type 2 - genetics / Glucose Transporter Type 2 - metabolism / Health aspects / hypoxia-inducible factor 1 / Immune response / Immune system / Immunity, Cellular / Immunosuppressive Agents - administration & dosage / Immunosuppressive Agents - pharmacology / Infections / Inhibition / Interleukin 13 / Interleukin 4 / Liposomes / Lymphocytes T / Macrophage Activation / Macrophages / Macrophages - drug effects / Macrophages - immunology / Medicine / Metabolism / Mice / Mice, Inbred BALB C / Mice, Knockout / nematode infections / Nematodes / Nippostrongylus - immunology / Nippostrongylus brasiliensis / Nutrition research / Permeability / phenotype / Protein Transport / Recruitment / Rodents / Roundworms / Small intestine / Sodium / Strongylida Infections - immunology / Strongylida Infections - metabolism / Transporter / Up-Regulation - immunology