NYMC Faculty Publications

Partial Restoration of Macrophage Alteration from Diet-Induced Obesity in Response to Porphyromonas Gingivalis Infection

Author Type(s)

Faculty

Additional Author Affiliation

Touro College of Dental Medicine at NYMC

DOI

10.1371/journal.pone.0070320

Journal Title

PLoS One

First Page

70320

Last Page

70320

Document Type

Article

Publication Date

1-1-2013

Department

Pathology, Microbiology and Immunology

Keywords

Animals, Arginase, Bacteroidaceae Infections, Diet, High-Fat, Gene Expression Profiling, Immunophenotyping, Macrophages, Mice, Obesity, Phenotype, Porphyromonas gingivalis, Reproducibility of Results, Signal Transduction, Thrombospondin 1

Disciplines

Medicine and Health Sciences

Abstract

Obesity is a chronic inflammatory disease that weakens macrophage innate immune response to infections. Since M1 polarization is crucial during acute infectious diseases, we hypothesized that diet-induced obesity inhibits M1 polarization of macrophages in the response to bacterial infections. Bone marrow macrophages (BMMΦ) from lean and obese mice were exposed to live Porphyromonas gingivalis (P. gingivalis) for three incubation times (1 h, 4 h and 24 h). Flow cytometry analysis revealed that the M1 polarization was inhibited after P. gingivalis exposure in BMMΦ from obese mice when compared with BMMΦ from lean counterparts. Using a computational approach in conjunction with microarray data, we identified switching genes that may differentially control the behavior of response pathways in macrophages from lean and obese mice. The two most prominent switching genes were thrombospondin 1 and arginase 1. Protein expression levels of both genes were higher in obese BMMΦ than in lean BMMΦ after exposure to P. gingivalis. Inhibition of either thrombospondin 1 or arginase 1 by specific inhibitors recovered the M1 polarization of BMMΦ from obese mice after P. gingivalis exposure. These data indicate that thrombospondin 1 and arginase 1 are important bacterial response genes, whose regulation is altered in macrophages from obese mice.

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