A mouse-adapted Staphylococcus aureus strain enables lifelong neonatal colonization and elicits a Th17-dominated immune response
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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 .
Author summary
Up to 20% of the population carry the bacterium Staphylococcus aureus in their nose for months or years, usually without symptoms. When the immune system is weakened, however, these bacteria can cause serious infections. Therefore, it is important to understand how our immune system recognizes S. aureus during colonization — and how the bacterium persists despite this.
Research in this area has long been hampered by the lack of animal models that reliably reproduce long-term colonization. We addressed this using a mouse-adapted S. aureus strain, JSNZ, which colonized adult mice for several weeks. Colonized parents transmitted the strain to their neonates who then carry the bacteria for their lifetime. They had reduced nasal levels of immune-cell recruiting proteins (chemokines), which may have contributed to prolonged bacterial persistence. Both neonatal and adult colonization triggered a strong, lasting immune response dominated by Th17 cells. This response was comparable regardless of whether colonization occurred in early life or adulthood.
This model offers a physiologically relevant tool to study S. aureus -immune system interactions during colonization, advancing our understanding of infection risk and potential preventive strategies.
