Related Experiment Video
Updated: Jul 6, 2026
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
TLR2-dependent MyD88 signaling contributes to early host defense in murine Enterococcus faecium peritonitis
Masja Leendertse1, Rob J L Willems, Ida A J Giebelen
1Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. m.leendertse@amc.uva.nl
Abstract:
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.
Insights
MyD88 adaptor protein and TLR2 are crucial for host defense against Enterococcus faecium peritonitis, facilitating neutrophil recruitment and bacterial clearance. TLR4 plays no significant role in this immune response.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Enterococcus faecium infections are a growing global health concern.
- Toll-like receptors (TLRs) are vital for pathogen recognition and initiating innate immune responses.
- Understanding host defense mechanisms against E. faecium is critical for developing effective treatments.
Purpose of the Study:
- To investigate the roles of MyD88, TLR2, TLR4, and CD14 in host defense against E. faecium peritonitis.
- To elucidate the signaling pathways involved in the innate immune response to E. faecium.
Main Methods:
- Utilized MyD88, TLR2, TLR4, and CD14 knockout (KO) mouse models.
- Assessed bacterial loads, neutrophil influx, and macrophage responsiveness in vitro and in vivo.
- Employed human embryonic kidney 293 cells for transfection studies.
Main Results:
- MyD88 KO mice showed impaired early response, higher bacterial loads, and reduced neutrophil influx.
- Macrophages from MyD88, TLR2, and CD14 KO mice exhibited reduced responsiveness to E. faecium.
- TLR2 KO mice had increased bacterial loads and diminished neutrophil influx, while CD14 KO mice showed no significant difference.
- TLR4 was found to play no role in the immune response to E. faecium.
Conclusions:
- MyD88 is essential for effective host defense against E. faecium peritonitis, partly through TLR2.
- MyD88 and TLR2 facilitate neutrophil recruitment to the infection site.
- CD14 contributes to macrophage responsiveness, but its role in vivo is less pronounced than MyD88 or TLR2.
