S.aureus may induce an immune phenotype to promote its persistent colonisation of the nose and impact vaccine efficacy. Thus, a greater understanding of the interaction of S.aureus with the immune system during colonisation is required. Immune training is a process that imprints a phenotype on innate immune cells, like monocytes, which alter subsequent responses of the cell. Here we explore the capacity of S.aureus to train monocytes with an aim to understand how it may impact colonisation and vaccine efficacy.
Human monocytes, isolated from buffy coats, were trained by exposure to S.aureus for 24hr then removed. The monocytes were rested for 6 days before restimulation with LPS.  S.aureus trained monocytes produced significantly more IL-10, TNF and IL-6, measured by ELISA and RT-PCR, in response to LPS when compared to naive monocytes. S.aureus trained monocytes displayed a shift towards more glycolytic energy production compared to naïve monocytes; demonstrating an increased expression of mTOR and phospho-S6 activity. Epigenetic changes underpin the immune training seen in monocytes, which are driven through the activity of methyltransferases, acetyltransferases, and histone deacetylases. When the monocytes are incubated in the presence of the acetyltransferase inhibitor, ECGC, or the methyltransferase inhibitor, MTA, during training the inflammatory response is dampened compared to the conventionally S.aureustrained cells. Suggesting the requirement of epigenetic modifications to imprint the S.aureus trained immunity phenotype.
These data suggest S.aureus has the potential to imprint a trained immunity phenotype in monocytes. In particular the increased IL-10 response in S.aureus trained monocytes, suggests that this immune training might be associated with a more immunosuppressive phenotype. This could have significant consequences for S.aureus nasal colonisation, persistence and possibly vaccine efficacy.

_S.aureus_ may induce an immune phenotype to promote its persistent colonisation of the nose and impact vaccine efficacy. Thus, a greater understanding of the interaction of _S.aureus_ with the immune system during colonisation is required. Immune training is a process that imprints a phenotype on innate immune cells, like monocytes, which alter subsequent responses of the cell. Here we explore the capacity of _S.aureus_ to train monocytes with an aim to understand how it may impact colonisation and vaccine efficacy.
Human monocytes, isolated from buffy coats, were trained by exposure to _S.aureus_ for 24hr then removed. The monocytes were rested for 6 days before restimulation with LPS.  _S.aureus_ trained monocytes produced significantly more IL-10, TNF and IL-6, measured by ELISA and RT-PCR, in response to LPS when compared to naive monocytes. _S.aureus_ trained monocytes displayed a shift towards more glycolytic energy production compared to naïve monocytes; demonstrating an increased expression of mTOR and phospho-S6 activity. Epigenetic changes underpin the immune training seen in monocytes, which are driven through the activity of methyltransferases, acetyltransferases, and histone deacetylases. When the monocytes are incubated in the presence of the acetyltransferase inhibitor, ECGC, or the methyltransferase inhibitor, MTA, during training the inflammatory response is dampened compared to the conventionally _S.aureus_trained cells. Suggesting the requirement of epigenetic modifications to imprint the _S.aureus_ trained immunity phenotype.
These data suggest _S.aureus_ has the potential to imprint a trained immunity phenotype in monocytes. In particular the increased IL-10 response in _S.aureus_ trained monocytes, suggests that this immune training might be associated with a more immunosuppressive phenotype. This could have significant consequences for _S.aureus_ nasal colonisation, persistence and possibly vaccine efficacy.

Investigating S.aureus induced immune training to understand its implication during nasal colonisation

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