title: An optimized, fast-to-perform mouse lung infection model with the human pathogen Chlamydia trachomatis for in vivo screening of antibiotics, vaccine candidates and modified host-pathogen interactions.
abstract: Chlamydia trachomatis causes sexually transmitted diseases with infertility, pelvic inflammatory disease and neonatal pneumonia as complications. The duration of urogenital mouse models with the strict mouse pathogen C. muridarum addressing vaginal shedding, pathological changes of the upper genital tract or infertility is rather long. Moreover, vaginal C. trachomatis application usually does not lead to the complications feared in women. A fast-to-perform mouse model is urgently needed to analyze new antibiotics, vaccine candidates, immune responses (in gene knockout animals) or mutants of C. trachomatis. To complement the valuable urogenital model with a much faster and quantifiable screening method, we established an optimized lung infection model for the human intracellular bacterium C. trachomatis serovar D (and L2) in immunocompetent C57BL/6J mice. We demonstrated its usefulness by sensitive determination of antibiotic effects characterizing advantages and limitations achievable by early or delayed short tetracycline treatment and single-dose azithromycin application. Moreover, we achieved partial acquired protection in reinfection with serovar D indicating usability for vaccine studies, and showed a different course of disease in absence of complement factor C3. Sensitive monitoring parameters were survival rate, body weight, clinical score, bacterial load, histological score, the granulocyte marker myeloperoxidase, IFN-γ, TNF-α, MCP-1 and IL-6.
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dutow
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Wask
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bothe
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Fehlhaber
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Laudeley
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rheinheimer
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Zhangsheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Institute for Laboratory Animal Science, Medical School Hannover (MHH), D-30625 Hannover, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.affiliation: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, D-30625 Hannover, Germany klos.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000276:immunology*; D001706:Biopsy; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000502:physiology*; D061387:Chlamydial Pneumonia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D003176:Complement C3; D016207:Cytokines; D007074:Immunoglobulin G; D009195:Peroxidase
keywords: Chlamydia trachomatis; antibiotic treatment; azithromycin; complement; gene knockout mice; mouse model; pneumonia; screening; tetracycline; vaccine