| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Center for Infection and Immunity Amsterdam,
Center for Experimental and Molecular Medicine, and
Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands; and
Eijkman-Winkler Institute for Medical Microbiology, Infectious Diseases and Inflammation, University Medical Center, Utrecht, The Netherlands
The incidence of infections with Enterococcus faecium is increasing worldwide. TLRs have been implicated in the recognition of pathogens and the initiation of an adequate innate immune response. We here sought to determine the roles of MyD88, the common adaptor protein involved in TLR signaling, TLR2, TLR4, and CD14 in host defense against E. faecium peritonitis. MyD88 knockout (KO) mice demonstrated an impaired early response to E. faecium peritonitis, as reflected by higher bacterial loads in peritoneal fluid and liver accompanied by a markedly attenuated neutrophil influx into the abdominal cavity. In vitro, not only MyD88 KO macrophages but also TLR2 KO and CD14 KO macrophages displayed a reduced responsiveness to E. faecium. In accordance, transfection of TLR2 rendered human embryonic kidney 293 cells responsive to E. faecium, which was enhanced by cotransfection of CD14. TLR2 KO mice showed higher bacterial loads in peritoneal fluid after in vivo infection with E. faecium and a diminished influx of neutrophils, whereas CD14 KO mice had an unaltered host response. E. faecium phagocytosis and killing were not affected by MyD88, TLR2, or CD14 deficiency. TLR4 did not play a role in the immune response to E. faecium in vitro or in vivo. These data suggest that MyD88 contributes to the effective clearance of E. faecium during peritonitis at least in part via TLR2 and by facilitating neutrophil recruitment to the site of the infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Masja Leendertse, Center for Experimental and Molecular Medicine, Academic Medical Center, G2–130, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail address: m.leendertse{at}amc.uva.nl
2 Abbreviations used in this paper: CC17, clonal complex-17; PAMP, pathogen-associated molecular pattern; LTA, lipoteichoic acid; WT, wild type; KO, knockout; LIX, LPS-induced CXC chemokine; ASAT, aspartate aminotransferase; ALAT, alanine aminotransferase; HEK, human embryonic kidney.
This article has been cited by other articles:
|
|
 |
|
  L. R. Thurlow, V. C. Thomas, S. D. Fleming, and L. E. Hancock Enterococcus faecalis Capsular Polysaccharide Serotypes C and D and Their Contributions to Host Innate Immune Evasion Infect. Immun., December 1, 2009; 77(12): 5551 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Thurlow, V. C. Thomas, and L. E. Hancock Capsular Polysaccharide Production in Enterococcus faecalis and Contribution of CpsF to Capsule Serospecificity J. Bacteriol., October 15, 2009; 191(20): 6203 - 6210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leichtle, M. Hernandez, K. Pak, K. Yamasaki, C.-F. Cheng, N. J. Webster, A. F. Ryan, and S. I. Wasserman TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media Innate Immunity, August 1, 2009; 15(4): 205 - 215. [Abstract] [PDF]
|
|
|
|
 |
|
 F. P. Baqai, D. S. Gridley, J. M. Slater, X. Luo-Owen, L. S. Stodieck, V. Ferguson, S. K. Chapes, and M. J. Pecaut Effects of spaceflight on innate immune function and antioxidant gene expression J Appl Physiol, June 1, 2009; 106(6): 1935 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Leendertse, R. J.L. Willems, I. A.J. Giebelen, J. J.T.H. Roelofs, N. van Rooijen, M. J.M. Bonten, and T. van der Poll Peritoneal macrophages are important for the early containment of Enterococcus faecium peritonitis in mice Innate Immunity, February 1, 2009; 15(1): 3 - 12. [Abstract] [PDF]
|
|
|
|
|
|
M. Leendertse, R. J. L. Willems, I. A. J. Giebelen, J. J. T. H. Roelofs, M. J. M. Bonten, and T. van der Poll Neutrophils Are Essential for Rapid Clearance of Enterococcus faecium in Mice Infect. Immun., January 1, 2009; 77(1): 485 - 491. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
