TY - JOUR
T1 - 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
AU - Dutow, Pavel
AU - Wask, Lea
AU - Bothe, Miriam
AU - Fehlhaber, Beate
AU - Laudeley, Robert
AU - Rheinheimer, Claudia
AU - Yang, Zhangsheng
AU - Zhong, Guangming
AU - Glage, Silke
AU - Klos, Andreas
N1 - Publisher Copyright:
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PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Chlamydia trachomatis
KW - antibiotic treatment
KW - azithromycin
KW - complement
KW - gene knockout mice
KW - mouse model
KW - pneumonia
KW - screening
KW - tetracycline
KW - vaccine
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U2 - 10.1093/femspd/ftv120
DO - 10.1093/femspd/ftv120
M3 - Article
C2 - 26676260
AN - SCOPUS:84999630882
SN - 2049-632X
VL - 74
JO - Pathogens and disease
JF - Pathogens and disease
IS - 2
ER -