Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Skin Infection

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S. aureus infection has emerged in the past decade as a major burden to public health and is responsible for a surge in preclinical research. Mice are the most commonly studied animals for modeling of human S. aureus infection. However, it is increasingly evident that available murine models poorly mimic human S. aureus disease. Routinely, a supra-physiologic inoculum is required to establish soft-tissue pathology. Additionally, many S. aureus factors exhibit unique human tropism and cannot be adequately investigated in rodents. Here we investigated S. aureus infection in NSG mice engrafted with human umbilical CD34+ cells. We showed that a one to two log lower infectious inoculum of S. aureus establishes consistent skin lesions in humanized NSG mice. This inoculum is comparable to published inocula required to induce infection in humans. In addition, we showed that Panton-Valentine Leucocidin, a human tropic factor secreted by S. aureus, contributes to the development of dermonecrosis in the humanized mice, and its interaction with human neutrophils and human C5a receptor appears to be important for immunopathology. Overall our study suggests that humanized mice are an improved tool for modeling of human S. aureus infection.

Vyšlo v časopise: Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Skin Infection. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005292
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005292

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