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Basic sciences oral session 2–Immunity and animal models
O4-S2.01 The host response to chlamydial infection results in increased gonococcal colonisation in a novel coinfection model
  1. A Jerse1,
  2. R Vonck1,
  3. T Darville2
  1. 1Uniformed Services University, Bethesda, USA
  2. 2University of Pittsburgh Medical Center, Pittsburgh, USA


Objective Neisseria gonorrhoeae and Chlamydia trachomatis cause similar urogenital diseases and up to 70% of individuals with gonorrhoea also have chlamydia. Using a newly developed female mouse model of coinfection, we recently reported that higher numbers of N gonorrhoeae were recovered from mice with a pre-existing Chlamydia muridarum infection, the mouse strain of Chlamydia, compared to mice infected with N gonorrhoeae alone. Recent studies on the host response to N gonorrhoeae implicate toll-like receptor 4 (TLR4) and IL17 responses as being protective against N gonorrhoeae. Here we tested the hypothesis that the immune response to chlamydial infection makes the genital tract more permissive to N gonorrhoeae.

Methods Using an immune-targeted RT-PCR array we screened for alterations in host gene expression during chlamydial infection of BALB/c mice that may account for the observed increase in gonococcal colonisation. Mouse genital cells were collected by vaginal swab and analysed for TLR4 expression by flow cytometry. Coinfection studies were performed in BALB/cJ (TLR4 wild type) and C.C3-TLR4LPS-d/J (TLR4 mutant) mice and the number of viable chlamydiae and gonococci recovered from each group was determined by immunofluorescence using L929 cells and quantitative culture on GC agar, respectively.

Results Prior to N gonorrhoeae inoculation, mice with a pre-existing chlamydial infection had decreased expression of TLR4 and antimicrobial peptide (CRAMP, SLPI) genes. Consistent with the finding of decreased TLR4expression in coinfected mice, markers of inflammation (TLR2, TNFα, IL-1ß, platelet activating factor receptor [Pafr], and IL-23α) were up-regulated only in mice infected with N gonorrhoeae alone. A significantly lower percentage of TLR4-expressing epithelial cells was detected in vaginal swabs from chlamydia-infected wild-type mice prior to gonococcal challenge, and importantly, chlamydial infection did not enhance N gonorrhoeae infection of TLR4 mutant mice.

Conclusions These data suggest the host response to chlamydial infection creates an environment that is less protective against gonococcal infection by down-regulating the expression of TLR4 and antimicrobial peptides. This work therefore further illuminates the basis of this interesting consequence of coinfection and may also help direct the development of immunomodulatory therapies against this common coinfection and its consequences on reproductive health.

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