Publication: The role of NOD2 in murine and human melioidosis
Issued Date
2014-01-01
Resource Type
ISSN
15506606
00221767
00221767
Other identifier(s)
2-s2.0-84891122272
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Immunology. Vol.192, No.1 (2014), 300-307
Suggested Citation
Nicolle D. Myers, Narisara Chantratita, William R. Berrington, Wirongrong Chierakul, Direk Limmathurotsakul, Vanaporn Wuthiekanun, Johanna D. Robertson, H. Denny Liggitt, Sharon J. Peacock, Shawn J. Skerrett, T. Eoin West The role of NOD2 in murine and human melioidosis. Journal of Immunology. Vol.192, No.1 (2014), 300-307. doi:10.4049/jimmunol.1301633 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34049
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
The role of NOD2 in murine and human melioidosis
Abstract
Nucleotide-binding oligomerization domain 2 (NOD2) is a cytosolic pathogen recognition receptor that regulates susceptibility to a variety of infections and chronic diseases. Burkholderia pseudomallei, a facultative intracellular bacterium, causes the tropical infection melioidosis.We hypothesized that NOD2 may participate in host defense in melioidosis. We performed a series of in vitro assays and in vivo experiments and analyzed the association of human genetic variation with infection to delineate the contribution of NOD2 to the host response to B. pseudomallei. We found that transfection with NOD2 mediated NF-κB activation induced by B. pseudomallei stimulation of HEK293 cells. After low-dose inoculation with aerosolized B. pseudomallei, Nod2-deficient mice showed impaired clinical responses and permitted greater bacterial replication in the lung and dissemination to the spleen compared with wild-type mice. IL-6 and KC levels were higher in the lungs of Nod2-deficient mice. In a cohort of 1562 Thai subjects, a common genetic polymorphism in the NOD2 region, rs7194886, was associated with melioidosis, and this effect was most pronounced in women. rs7194886 was not associated with differences in cytokine production induced by whole-blood stimulation with the NOD2 ligand, muramyl dipeptide, or B. pseudomallei. To our knowledge, these findings are the first to characterize the role of NOD2 in host defense in mammalian melioidosis. Copyright © 2013 by The American Association of Immunologists, Inc.