title: Increased expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental Rickettsia conorii infection.
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.
authors: Institute of Clinical Medicine, Akershus University Hospital, Sykehusveien 25, Lørenskog 1478, Norway. elisabeth.astrup@rr-research.no.
authors: Elisabeth
authors: E
authors: Astrup
authors: Trine
authors: T
authors: Ranheim
authors: Jan K
authors: JK
authors: Damås
authors: Giovanni
authors: G
authors: Davì
authors: Francesca
authors: F
authors: Santilli
authors: Mogens
authors: M
authors: Jensenius
authors: Giustina
authors: G
authors: Vitale
authors: Pål
authors: P
authors: Aukrust
authors: Juan P
authors: JP
authors: Olano
authors: Kari
authors: K
authors: Otterdal
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D054415:Chemokine CCL19 / Q000097:blood* / Q000235:genetics; D054421:Chemokine CCL21 / Q000097:blood* / Q000235:genetics; D005260:Female; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000097:blood / Q000235:genetics; D012282:Rickettsia Infections / Q000097:blood* / Q000235:genetics / Q000382:microbiology; D020114:Rickettsia conorii / Q000502:physiology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7