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Open Access Highly Accessed Research article

Increased expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental Rickettsia conorii infection

Elisabeth Astrup12*, Trine Ranheim25, Jan K Damås67, Giovanni Davì8, Francesca Santilli8, Mogens Jensenius4, Giustina Vitale9, Pål Aukrust235, Juan P Olano10 and Kari Otterdal25

Author Affiliations

1 Institute of Clinical Medicine, Akershus University Hospital, Sykehusveien 25, Lørenskog 1478, Norway

2 Research Institute of Internal Medicine, Sognsvannsveien 20, 0372 Oslo, Norway

3 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, Oslo 0372, Norway

4 Department of Infectious Diseases, Oslo University Hospital Ullevål, Kirkeveien 166, Oslo 0450, Norway

5 Faculty of Medicine, University of Oslo, Pb 1078 Blidern, Oslo 0316, Norway

6 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Prinsesse Kristinas gate 3, Trondheim 7030, Norway

7 Department of Infectious Diseases, St. Olavs Hospital, Prinsesse Kristinas gate 3, Trondheim 7030, Norway

8 Center of Excellence on Aging, University of Chieti, Via Colle dell'Ara, 66013 Chieti, Italy

9 Department of Clinical Medicine and Pathology, School of Medicine, University of Palermo, Palermo 90133, Italy

10 Department of Pathology, University of Texas Medical Branch, Galveston, 301 University Blvd, TX 77555-0428, USA

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BMC Infectious Diseases 2014, 14:70  doi:10.1186/1471-2334-14-70

Published: 9 February 2014

Abstract

Background

Based on their essential role in concerting immunological and inflammatory responses we hypothesized that the homeostatic chemokines CCL19 and CCL21 may play a pathogenic role in rickettsiae infection.

Methods

Serum levels of CCL19 and CCL21 in patients with R. africae and R. conorii infection were analyzed by enzyme immunoassays. Lungs from R. conorii infected mice were examined for CCL19, CCL21 and CCR7 expression by immunohistochemistry.

Results

We found that patients with R. africae infection (n = 15) and in particular those with R. conorii infection (n = 16) had elevated serum levels of CCL19 on admission, with a decline during follow-up. While a similar pattern was seen for CCL21 in R. africae infection, patients with R. conorii infection showed persistently increased CCL21 levels during follow-up. In experimental R. conorii infection, we found strong immunostaining of CCL19 and CCL21 in the lungs, particularly in individuals that had received lethal doses. Immunofluorescence showed co-localization of CCR7 to endothelial cells, macrophages and fibroblasts within the lung tissue of R. conorii infected mice.

Conclusions

Our findings suggest that the CCL19/CCL21/CCR7 axis is up-regulated during R. africae and in particular during R. conorii infection, which may potentially contribute to the pathogenesis of these disorders.

Keywords:
Inflammation; Chemokines; CCR7; R. conorii; R. africae