Nonmenstrual toxic shock syndrome (nmTSS), linked to TSST-1-producing CC30 Staphylococcus aureus, is the leading manifestation of toxic shock syndrome (TSS). Due to case rarity and a lack of tractable animal models, TSS pathogenesis is poorly understood. We developed an S. aureus abscess model in HLA class II transgenic mice to investigate pathogenesis and treatment. TSST-1 sensitivity was established using murine spleen cell proliferation assays and cytokine assays following TSST-1 injection in vivo. HLA-DQ8 mice were infected subcutaneously with a tstpositive CC30 methicillin-sensitive S. aureus clinical TSS-associated isolate. Mice received intraperitoneal flucloxacillin, clindamycin, flucloxacillin and clindamycin, or a control reagent. Abscess size, bacterial counts, TSST-1 expression, and TSST-1 bioactivity were measured in tissues. Antibiotic effects were compared with the effects of control reagent. Purified TSST-1 expanded HLA-DQ8 T-cell Vβ subsets 3 and 13 in vitro and instigated cytokine release in vivo, confirming TSST-1 sensitivity. TSST-1 was detected in abscesses (0 to 8.0 μg/ml) and draining lymph nodes (0 to 0.2 μg/ ml) of infected mice. Interleukin 6 (IL-6), gamma interferon (IFN-γ), KC (CXCL1), and MCP-1 were consistent markers of inflammation during infection. Clindamycincontaining antibiotic regimens reduced abscess size and TSST-1 production. Infection led to detectable TSST-1 in soft tissues, and TSST-1 was detected in draining lymph nodes, events which may be pivotal to TSS pathogenesis. The reduction in TSST-1 production and lesion size after a single dose of clindamycin underscores a potential role for adjunctive clindamycin at the start of treatment of patients suspected of having TSS to alter disease progression.
Bibliographical noteFunding Information:
We acknowledge D. Kioussis and R. A. Flavell for transgenic mice and D. M. Altmann for access, and we thank Nur S. C. Ahmad for technical contributions. We acknowledge support from the NIHR Biomedical Research Centre (BRC) to the Imperial College Healthcare Trust and the NIHR BRC-funded Tissue Bank. This work was also supported by the UK Clinical Research Collaboration through a research training fellowship (G0800777/1 to H.S.). We have no conflicts of interest to declare.
© 2019 Sharma et al.
- Nonmenstrual toxic shock syndrome
- Staphylococcus aureus
- Transgenic mice