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Relative chemokine and adhesion molecule expression in Mediterranean spotted fever and African tick bite fever
Jan K Damås1, Giovanni Davì, Mogens Jensenius
1Research Institute for Internal Medicine, Rikshospitalet University Hospital, 0027 Oslo, Norway. jan.k.damas@ntnu.no
Objectives:
Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii) is a potential lethal disease while African tick bite fever (ATBF) caused by Rickettsia africae is a self-limiting flu-like illness. We hypothesized that different inflammatory potential in endothelial cells could contribute to the different clinical features in these rickettsioses.
Methods:
We analyzed the effect of heat-inactivated R. africae and R. conorii on the mRNA and protein levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and adhesion molecules in endothelial cells. Serum samples from patients with MSF (n=16) and ATBF (n=15) were collected before and after therapy.
Results:
R. conorii induced a marked increase in MCP-1, IL-8, and adhesion molecules in endothelial cells, involving toll-like receptor 4 activation. In contrast, R. africae induced MCP-1 expression, but only modest or no responses were seen on IL-8 and adhesion molecules. Comparable to the in vitro response, levels of IL-8 and adhesion molecules showed no or only a modest increase in ATBF patients while these inflammatory markers were markedly elevated during MSF.
Conclusions:
Our findings suggest a superior inflammatory potential of R. conorii as compared to R. africae in endothelial cells, potentially related to the more severe inflammation in MSF comparing ATBF.
Insights
Mediterranean spotted fever (MSF) caused by Rickettsia conorii is severe, while African tick bite fever (ATBF) caused by Rickettsia africae is mild. R. conorii triggers greater inflammation in endothelial cells, explaining MSF
Area of Science:
- Infectious Diseases
- Immunology
- Cell Biology
Background:
- Mediterranean spotted fever (MSF) and African tick bite fever (ATBF) are distinct rickettsioses with differing clinical severity.
- Rickettsia conorii causes MSF, a potentially lethal disease, while Rickettsia africae causes ATBF, a self-limiting illness.
Purpose of the Study:
- To investigate the differential inflammatory potential of R. conorii and R. africae in endothelial cells.
- To correlate in vitro findings with clinical inflammatory marker levels in patients with MSF and ATBF.
Main Methods:
- Assessed mRNA and protein levels of MCP-1, IL-8, and adhesion molecules in endothelial cells stimulated with heat-inactivated R. africae and R. conorii.
- Analyzed serum samples from MSF and ATBF patients for inflammatory markers before and after therapy.
Main Results:
- R. conorii significantly upregulated MCP-1, IL-8, and adhesion molecules in endothelial cells via TLR4 activation.
- R. africae induced MCP-1 but had minimal effects on IL-8 and adhesion molecules.
- Elevated IL-8 and adhesion molecule levels in MSF patients mirrored the in vitro pro-inflammatory response of R. conorii, unlike in ATBF patients.
Conclusions:
- R. conorii exhibits a stronger inflammatory potential in endothelial cells compared to R. africae.
- This differential inflammatory response likely contributes to the distinct clinical severity observed in MSF and ATBF.
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