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CD14 impairs host defense against gram-negative sepsis caused by Burkholderia pseudomallei in mice.
J Infect Dis. 2008 Nov 01; 198(9):1388-97.JI

Abstract

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.

Authors+Show Affiliations

Centers for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. w.j.wiersinga@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18855560

Citation

Wiersinga, W Joost, et al. "CD14 Impairs Host Defense Against Gram-negative Sepsis Caused By Burkholderia Pseudomallei in Mice." The Journal of Infectious Diseases, vol. 198, no. 9, 2008, pp. 1388-97.
Wiersinga WJ, de Vos AF, Wieland CW, et al. CD14 impairs host defense against gram-negative sepsis caused by Burkholderia pseudomallei in mice. J Infect Dis. 2008;198(9):1388-97.
Wiersinga, W. J., de Vos, A. F., Wieland, C. W., Leendertse, M., Roelofs, J. J., & van der Poll, T. (2008). CD14 impairs host defense against gram-negative sepsis caused by Burkholderia pseudomallei in mice. The Journal of Infectious Diseases, 198(9), 1388-97. https://doi.org/10.1086/592220
Wiersinga WJ, et al. CD14 Impairs Host Defense Against Gram-negative Sepsis Caused By Burkholderia Pseudomallei in Mice. J Infect Dis. 2008 Nov 1;198(9):1388-97. PubMed PMID: 18855560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD14 impairs host defense against gram-negative sepsis caused by Burkholderia pseudomallei in mice. AU - Wiersinga,W Joost, AU - de Vos,Alex F, AU - Wieland,Catharina W, AU - Leendertse,Masja, AU - Roelofs,Joris J T H, AU - van der Poll,Tom, PY - 2008/10/16/pubmed PY - 2008/12/17/medline PY - 2008/10/16/entrez SP - 1388 EP - 97 JF - The Journal of infectious diseases JO - J Infect Dis VL - 198 IS - 9 N2 - 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. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/18855560/CD14_impairs_host_defense_against_gram_negative_sepsis_caused_by_Burkholderia_pseudomallei_in_mice_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/592220 DB - PRIME DP - Unbound Medicine ER -