title: The complement C3a receptor is critical in defense against Chlamydia psittaci in mouse lung infection and required for antibody and optimal T cell response.
abstract: BACKGROUND
  The complement system protects against extracellular pathogens and links innate and adaptive immunity. In this study, we investigated the anaphylatoxin C3a receptor (C3aR) in Chlamydia psittaci lung infection and elucidated C3a-dependent adaptive immune mechanisms.
  
  
  METHODS
  Survival, body weight, and clinical score were monitored in primary mouse infection and after serum transfer. Bacterial load, histology, cellular distribution, cytokines, antibodies, and lymphocytes were analyzed.
  
  
  RESULTS
  C3aR(-/-) mice showed prolonged pneumonia with decreased survival, lower weight, and higher clinical score. Compared to wild-type mice bacterial clearance was impaired, and inflammatory parameters were increased. In lung-draining lymph nodes of C3aR(-/-) mice the total number of B cells, CD4(+) T cells, and Chlamydia-specific IFN-γ(+) (CD4(+) or CD8(+)) cells was reduced upon infection, and the mice were incapable of Chlamydia-specific immunoglobulin M or immunoglobulin G production. Performed before infection, transfer of hyperimmune serum prolonged survival of C3aR(-/-) mice.
  
  
  CONCLUSIONS
  C3a and its receptor are critical for defense against C. psittaci in mouse lung infection. In this model, C3a acts via its receptor as immune modulator. Enhancement of specific B and T cell responses upon infection with an intracellular bacterium were identified as hitherto unknown features of C3a/C3aR. These new functions might be of general immunological importance.
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH).
authors.forename: Pavel
authors.initials: P
authors.lastname: Dutow
authors.forename: Beate
authors.initials: B
authors.lastname: Fehlhaber
authors.forename: Jenny
authors.initials: J
authors.lastname: Bode
authors.forename: Robert
authors.initials: R
authors.lastname: Laudeley
authors.forename: Claudia
authors.initials: C
authors.lastname: Rheinheimer
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.forename: Andreas
authors.initials: A
authors.lastname: Klos
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D023521:Chlamydophila Infections / Q000276:immunology / Q000517:prevention & control*; D002691:Chlamydophila psittaci / Q000472:pathogenicity*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008168:Lung / Q000382:microbiology*; D008297:Male; D051379:Mice; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control*; D011951:Receptors, Complement / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011951:Receptors, Complement; C085567:complement C3a receptor
keywords: C3a receptor; Chlamydia psittaci; adaptive immunity; anaphylatoxin; bacterium; chlamydia; complement; defense; intracellular