A mouse-adapted Staphylococcus aureus strain enables lifelong neonatal colonization and elicits a Th17-dominated immune response

Abstract

The opportunistic pathogen Staphylococcus aureus persistently colonizes the anterior nares of up to 20% of the human population, yet there were no persistent mouse colonization models to study host-pathogen interaction. Using the mouse-adapted S. aureus strain JSNZ (CC88-MSSA), we established a neonatal S. aureus colonization model in C57BL/6N mice. Natural neonatal colonization was achieved by vertical transmission in a JSNZ-positive breeding colony. Offspring were followed for up to 69 weeks and found persistently colonized in the nose and cecum with high bacterial loads. Adult mice were colonized by intranasal inoculation of JSNZ; controls received PBS. The colonization patterns and the S. aureus-specific T cell responses were then monitored over a period of 28 days and compared between age-matched mice colonized as neonates or adults. The neonatal group remained persistently colonized in nose and gut with high bacterial densities. In contrast, mice colonized as adults had lower and declining bacterial loads in the nose. Some eliminated S. aureus from the nares, while all remained colonized in the gut. Neonatally colonized mice exhibited reduced nasal chemokine levels, which may have favored the prolonged S. aureus persistence. Ex vivo re-stimulation of cervical lymph node cells with an S. aureus antigen cocktail revealed a Th17-dominated antigen-specific T cell response in both colonized groups. The lymph node cells secreted large amounts of IL-17, but Th1-, Th2-associated and regulatory cytokines were also detected. The cytokine patterns were similar in both colonized groups except for IL-5, which was more abundant upon neonatal colonization. In conclusion, vertical transmission of the mouse-adapted S. aureus strain JSNZ reliably establishes persistent high-density neonatal colonization, providing a physiologically relevant model for the study of S. aureus host interactions. Route and timing of colonization do not fundamentally affect the T cell response to S. aureus.