TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas MyD88 is required to clear infection.
Porphyromonas gingivalis is a gram-negative anaerobe considered to be a major periodontal pathogen. TLR2 plays a central role in the response to P. gingivalis infection in vivo. In its absence there is a weak inflammatory response; however, bacteria are cleared rapidly compared with wild-type mice. We examined the role of the TLR adaptor proteins MyD88 and TLR/IL-1R-domain-containing adaptor-inducing IFN-beta in the inflammatory response to P. gingivalis in vivo and in the ability to clear the bacterial infection. Proinflammatory cytokine production in response to P. gingivalis infection depends on TLR2, but it does not require MyD88 or TLR/IL-1R-domain-containing adaptor-inducing IFN-beta. In contrast, the generation of intracellular toxic oxygen species and the ultimate clearance of P. gingivalis infection depend critically on MyD88, independent of TLR2. Thus, robust cytokine production and bacterial clearance are independent events mediated by distinct signaling pathways following infection with P. gingivalis.
Burns
Elia
E
Institute of Dental Sciences, Faculty of Dental Medicine, Hadassah and Hebrew University Medical Center, Jerusalem, Israel.
Eliyahu
Tal
T
Uematsu
Satoshi
S
Akira
Shizuo
S
Nussbaum
Gabriel
G
D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D018836:Inflammation Mediators; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2