Ready, STAT3, Go! Bacteria in the race for M2 macrophage polarisation

Despite macrophages representing professional immune cells that are integral to the host defences against microbial threats, several intracellular bacteria not only infect, but survive, replicate and often persist in these cells. This is perhaps possible because not all macrophages are the same. Instead, macrophages are loosely divided into two classes: the M1 'classically activated' pro-inflammatory subset and the M2 'alternatively activated' cells that are generally anti-inflammatory and infection-permissive. In this review, we summarise recent findings explaining how several intracellular pathogens, often using secreted effectors, rewire host circuitry in favour of an anti-inflammatory niche. A common theme is the phosphorylation and activation of the signal transducer and activator of transcription-3 (STAT3) transcription factor. We describe and compare the diverse mechanisms employed and reflect how such non-canonical processes may have evolved to circumvent regulation by the host, providing a potent means by which different pathogens manipulate the cells they infect.

Automated summary

Despite being important for host defences, some intracellular bacteria are able to infect, survive, replicate, and persist in macrophages. This may be due to the heterogeneity of macrophages, which can be divided into pro-inflammatory M1 subset and anti-inflammatory M2 subset. Recent findings suggest that intracellular pathogens can manipulate host cells by activating the STAT3 transcription factor through various mechanisms.