Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis

Maekawa, Tomoki, Krauss, Jennifer L., Abe, Toshiharu, Jotwani, Ravi, Triantafilou, Martha ORCID: https://orcid.org/0000-0002-7473-6278, Triantafilou, Kathy ORCID: https://orcid.org/0000-0002-7473-6278, Hashim, Ahmed, Hoch, Shifra, Curtis, Michael A., Nussbaum, Gabriel, Lambris, John D. and Hajishengallis, George 2014. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host and Microbe 15 (6) , pp. 768-778. 10.1016/j.chom.2014.05.012

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology
Publisher:	Elsevier
ISSN:	1931-3128
Date of Acceptance:	21 April 2014
Last Modified:	31 Oct 2022 08:59
URI:	https://orca.cardiff.ac.uk/id/eprint/79399

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