About this project
About this project
Monocytes and neutrophils are sentinel cells of innate immunity and are found in abundance during periodontal infection. We have found that the periodontal pathogen Porphyromonas gingivalis is phagocytosed by the monocytic cell line THP-1, inhibits the expression of the chemokine CXCL8 through gingipains and induces the formation of osteoclast-like polynuclear giant cells (Jayaprakash et al., 2014). This is interesting, since osteoclasts are active in tissue destruction, both in periodontitis and rheumatic diseases, and probably also in tissue remodelling in the atherosclerotic plaque. Future studies will focus on clarifying the signal transduction mechanisms in monocytes induced by P. gingivalis, the role of monocyte differentiation to osteoclast-like cells and the effects of P. gingivalis-modified LDL on foam cell formation.
We have studied the role of NETs (neutrophil extracellular traps) in P. gingivalis interaction with human neutrophils. NETs are a part of the innate immune response to infections and consist of a meshwork of DNA-fibers with histones and anti-microbial proteins. NETs is one of the first lines of defense against pathogens by binding various microorganisms, preventing them from spreading and ensuring killing through local concentration of antimicrobial agents. Findings show that wild-type P. gingivalis does not induce NET formation in neutrophils, however, mutants lacking gingipain R (Rgp) stimulate NET formation (Jayaprakash et al., 2015). This indicates that Rgp protects capture and killing of P. gingivalis through NETs. Whether NETs affect the inflammatory process in the atherosclerotic plaque and support thrombus formation will be investigated
- Jayaprakash, K., Khalaf, H., Bengtsson, T. (2014)Gingipains from Porphyromonas gingivalis play a significant role in induction and regulation of CXCL8 in THP-1 cells. BMC 14:193.
- Jayaprakash, K., Demirel, I., Khalaf, H., Bengtsson, T. (2015) The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis. Mol. Oral Microbiol. 30:361-375
- Jayaprakash, K., Demirel, I., Gunalty, S., Khalaf, H., Bengtsson, T. (2017) PKC, ERK/p38 MAP kinases and NFkB targeted signaling play a role in the expression and release of Il-1b and CXCL8 in Porphyromonas gingivalis-infected THP1 cells. APMIS 125:623-633