Send to

Choose Destination
Cell Host Microbe. 2014 Jun 11;15(6):768-78. doi: 10.1016/j.chom.2014.05.012.

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

Author information

University of Pennsylvania, School of Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
University of Louisville, Center for Oral Health and Systemic Disease, Louisville, KY 40292, USA.
Cardiff University School of Medicine, Institute of Infection and Immunity, Cardiff CF14 4XN, UK.
Queen Mary University of London, Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, London E1 2AT, UK.
Hebrew University, Hadassah Dental School, Jerusalem 12272, Israel.
University of Pennsylvania, Perelman School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA.
University of Pennsylvania, School of Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA. Electronic address:


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center