Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
6-11-2014
Publication Source
Cell Host & Microbe
Volume
15
Issue
6
Start Page
768
Last Page
778
DOI
10.1016/j.chom.2014.05.012
Abstract
Certain low-abundance bacterial species, such as the periodontitis-associated oral bacterium Porphyromonas gingivalis can subvert host immunity to remodel a normally symbiotic microbiota into a dysbiotic, disease-provoking state. However, such pathogens also exploit inflammation to thrive in dysbiotic conditions. How these bacteria evade immunity while maintaining inflammation is unclear. As previously reported, P. gingivalis remodels the oral microbiota into a dysbiotic state by exploiting complement. Now we show that in neutrophils P. gingivalis disarms a host-protective TLR2-MyD88 pathway via proteasomal degradation of MyD88, whereas it activates an alternate TLR2-Mal-PI3K pathway. This alternate TLR2-Mal-PI3K pathway blocks phagocytosis, provides ‘bystander’ protection to otherwise susceptible bacteria, and promotes dysbiotic inflammation in vivo. This mechanism to disengage bacterial clearance from inflammation required an intimate crosstalk between TLR2 and the complement receptor C5aR, and can contribute to the persistence of microbial communities that drive dysbiotic diseases.
Copyright/Permission Statement
© <2014>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Recommended Citation
Maekawa, T., Krauss, J. L., Abe, T., Jotwani, R., Triantafilou, M., Triantafilou, K., Hashim, A., Hoch, S., Curtis, M. A., Nussbaum, G., Lambris, J. D., & Hajishengallis, G. (2014). Porphyromonas Gingivalis Manipulates Complement and TLR Signaling to Uncouple Bacterial Clearance From Inflammation and Promote Dysbiosis. Cell Host & Microbe, 15 (6), 768-778. http://dx.doi.org/10.1016/j.chom.2014.05.012
Date Posted: 24 February 2022
This document has been peer reviewed.