Document Detail

CD14 impairs host defense against gram-negative sepsis caused by Burkholderia pseudomallei in mice.
MedLine Citation:
PMID:  18855560     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: CD14 is a pattern-recognition receptor that can facilitate the presentation of bacterial components to either Toll-like receptor 2 (TLR2) or TLR4. We have recently shown that during melioidosis, a severe infection caused by the gram-negative bacterium Burkholderia pseudomallei, TLR2 but not TLR4 impacts the immune response of the intact host in vivo. METHODS: The function of CD14 in melioidosis was analyzed by means of in vitro and in vivo approaches, using wild-type (WT) and CD14 knockout (KO) mice. RESULTS: CD14-deficient macrophages and whole blood leukocytes released less tumor necrosis factor (TNF)-alpha on stimulation with B. pseudomallei or B. pseudomallei lipopolysaccharide in vitro, compared with WT cells. Strikingly, CD14 KO mice intranasally inoculated with B. pseudomallei demonstrated reduced lethality and significantly decreased bacterial outgrowth, compared with WT mice. Administration of recombinant soluble CD14 to CD14 KO mice partially reversed their phenotype to that of WT mice. Lastly, CD14 deficiency did not alter the capacity of macrophages or neutrophils to phagocytose or kill B. pseudomallei. CONCLUSION: CD14 is crucially involved in the recognition of B. pseudomallei by innate immune cells but plays a remarkable detrimental role in the host response against B. pseudomallei. Inhibition of CD14 may be a novel treatment strategy in melioidosis.
W Joost Wiersinga; Alex F de Vos; Catharina W Wieland; Masja Leendertse; Joris J T H Roelofs; Tom van der Poll
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  198     ISSN:  0022-1899     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-15     Completed Date:  2008-12-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1388-97     Citation Subset:  AIM; IM    
Centers for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
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MeSH Terms
Antigens, CD14 / genetics*,  immunology
Burkholderia pseudomallei*
Kidney / pathology
Liver / pathology
Lung / cytology
Macrophages / physiology
Melioidosis / immunology*,  microbiology*,  pathology
Mice, Inbred C57BL
Mice, Knockout
Neutrophils / physiology
Phagocytosis / physiology
Pneumonia, Bacterial / pathology
Sepsis / immunology*
Reg. No./Substance:
0/Antigens, CD14

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