Publication: NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.
Accepted Date
2014-08-09
Issued Date
2014-09-18
Copyright Date
2014
Resource Type
Language
eng
ISSN
1935-2735 (electronic)
1935-2727 (printed)
1935-2727 (printed)
Rights
Mahidol University
Rights Holder(s)
PLoS neglected tropical diseases
Bibliographic Citation
West TE, Myers ND, Chantratita N, Chierakul W, Limmathurotsakul D, Wuthiekanun V, et al. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. PLoS Negl Trop Dis. 2014 Sep 18;8(9):e3178.
Suggested Citation
West, T. Eoin, Myers, Nicolle D., Narisara Chantratita, นริศรา จันทราทิตย์, Wirongrong Chierakul, วิรงค์รอง เจียรกุล, Direk Limmathurotsakul, ดิเรก ลิ้มมธุรสกุล, Vanaporn Wuthiekanun, วรรณพร วุฒิเอกอนันต์, Miao, Edward A., Hajjar, Adeline M., Peacock, Sharon J., Liggitt, H. Denny, Skerrett, Shawn J. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.. West TE, Myers ND, Chantratita N, Chierakul W, Limmathurotsakul D, Wuthiekanun V, et al. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. PLoS Negl Trop Dis. 2014 Sep 18;8(9):e3178.. doi:10.1371/journal.pntd.0003178. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/778
Research Projects
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Title
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.
Corresponding Author(s)
Other Contributor(s)
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit.
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.
Mahidol University. Faculty of Tropical Medicine. Department of Microbiology and Immunology.
Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene.
Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine.
Mahidol University. Faculty of Tropical Medicine. Department of Microbiology and Immunology.
Mahidol University. Faculty of Tropical Medicine. Department of Tropical Hygiene.
Abstract
Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is
a common manifestation of melioidosis and is associated with high mortality.
Understanding the key elements of host defense is essential to developing new
therapeutics for melioidosis. As a flagellated bacterium encoding type III
secretion systems, B. pseudomallei may trigger numerous host pathogen recognition
receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4,
along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome
in the cytoplasm that responds to flagellin (in mice) and type III secretion
system components (in mice and humans). In a murine model of respiratory
melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both
Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency
of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in
the lung much of this effect was attributable to Nlrc4, despite relative
preservation of pulmonary IL-1β production in Nlrc4(-/-) mice. Histologically,
deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than
deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated
with survival in melioidosis patients with pulmonary involvement. Co-inheritance
of rs6757121 and a functional TLR5 polymorphism had an additive effect on
survival. Our results show that NLRC4 and TLR5, key components of two flagellin
sensing pathways, each contribute to host defense in respiratory melioidosis.
