Humanized mice exhibit increased susceptibility to Staphylococcus aureus pneumonia.
J Infect Dis. 2016 Sep 16;
Authors: Prince A, Wang H, Kitur K, Parker D
Staphylococcus aureus is a highly successful human pathogen that has evolved in response to human immune pressure. The common USA300 MRSA strains express a number of toxins, such as the Panton-Valentine leukocidin and LukAB that have specificity for human receptors. Using NOD (non obese diabetic)-scid IL2Rγ(null) (NSG) mice reconstituted with a human hematopoietic system we were able to discriminate the roles of these toxins in the pathogenesis of pneumonia. We demonstrate that expression of human immune cells confers increased severity of USA300 infection. The expression of PVL but not LukAB resulted in more severe pulmonary infection by WT (30-fold higher cfus/ml, P<0.01) as compared with lukS/F-PV (Δpvl) infected mice. Treatment of mice with anti-PVL antibody also enhanced bacterial clearance. We found significantly greater (95% more, P<0.05) numbers of macrophages in the airways of mice infected with the Δpvl mutant versus the WT strain, as well as significantly greater expression of human TNF and IL-6 (84% and 51% respectively, P<0.01). These results suggest that the development of humanized mice may provide a framework to assess the contribution of human-specific toxins and better explore the roles of specific components of the human immune system in protection from S. aureus infection.
PMID: 27638942 [PubMed - as supplied by publisher]