title: A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci.
abstract: The complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present study, knockout mice lacking C3 and thus all main complement effector functions were intranasally infected with C. psittaci strain DC15. Clinical parameters, lung histology, and cytokine levels were determined. A subset of infections was additionally performed with mice lacking C5 or C5a receptors. Complement activation occurred before symptoms of pneumonia appeared. Mice lacking C3 were ∼100 times more susceptible to the intracellular bacteria compared to wild-type mice, with all C3(-/-) mice succumbing to infection after day 9. At a low infective dose, C3(-/-) mice became severely ill after an even longer delay, the kinetics suggesting a so far unknown link of complement to the adaptive, protective immune response against chlamydiae. The lethal phenotype of C3(-/-) mice is not based on differences in the anti-chlamydial IgG response (which is slightly delayed) as demonstrated by serum transfer experiments. In addition, during the first week of infection, the absence of C3 was associated with partial protection characterized by reduced weight loss, better clinical score and lower bacterial burden, which might be explained by a different mechanism. Lack of complement functions downstream of C5 had little effect. This study demonstrates for the first time a strong and complex influence of complement effector functions, downstream of C3 and upstream of C5, on the outcome of an infection with intracellular bacteria, such as C. psittaci.
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bode
authors.forename: Pavel
authors.initials: P
authors.lastname: Dutow
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sommer
authors.forename: Katrin
authors.initials: K
authors.lastname: Janik
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.forename: Antje
authors.initials: A
authors.lastname: Munder
authors.forename: Robert
authors.initials: R
authors.lastname: Laudeley
authors.forename: Konrad W
authors.initials: KW
authors.lastname: Sachse
authors.forename: Andreas
authors.initials: A
authors.lastname: Klos
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002691:Chlamydophila psittaci / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D009956:Psittacosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology
chemical_list: D003176:Complement C3; D003182:Complement C5; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011951:Receptors, Complement; D003165:Complement System Proteins; D009195:Peroxidase