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Abstract

infections have a high incidence of relapse due in part to the high levels of antibiotic persistence. It is known that growing and non-growing (e.g. persister) utilise the Pathogenicity Island 2 (SPI-2) Type 3 Secretion System (T3SS) to dampen the pro-inflammatory M1 state of macrophages and push the immune cells towards an anti-inflammatory M2 state. This allows prolonged survival in the host and facilitates relapse. However, this interplay between survival and macrophage activation states remains incompletely understood.

Here, I present a study on the influence of the initial phenotypic state of untreated (M0), IFN-γ (M1) and IL-4/IL-10 (M2) prepolarised differentiated murine bone marrow-derived macrophages (MΦs) on the survival and proliferation of Serovar (). As expected, pro-inflammatory M1 MΦs kill more efficiently than M0 cells. Surprisingly, shows decreased survival within anti-inflammatory M2 MΦs compared to M0 MΦs, which appears to be SPI-2 dependent. Further investigation revealed that even though induces SPI-2 T3SS within M1 and M2 prepolarised MΦs, the timing of SPI-2 activation is affected during infection of M2 MΦs, thereby reducing the ability of bacteria to proliferate. This leads to many more antibiotic tolerant non-growing surviving to combined antibiotic and macrophage challenges in prepolarised MΦs.

Together, these results suggest that infection of M0 MΦs followed by reprogramming to M2 MΦs appears to promote the optimal conditions for proliferation; nevertheless, non-growing cells may immediately persist and survive better in prepolarised MΦs.

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/content/journal/acmi/10.1099/acmi.mim2019.po0023
2020-01-01
2020-02-28
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.mim2019.po0023
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