Manipulation of Autophagy and Apoptosis Facilitates Intracellular Survival of in Human Neutrophils.

Polymorphonuclear neutrophils (PMN) are critical for first line innate immune defence against . Mature circulating PMN maintain a short half-life ending in constitutive apoptotic cell death. This makes them unlikely candidates as a bacterial intracellular niche. However, there is significant evidence to suggest that can survive intracellularly within PMN and this contributes to persistence and dissemination during infection. The precise mechanism by which parasitizes these cells remains to be established. Herein we propose a novel mechanism by which subverts both autophagy and apoptosis in PMN in order to maintain an intracellular survival niche during infection. Intracellular survival of within primary human PMN was associated with an accumulation of the autophagic flux markers LC3-II and p62, while inhibition of the autophagy pathway led to a significant reduction in intracellular survival of bacteria. This intracellular survival of was coupled with a delay in neutrophil apoptosis as well as increased expression of several anti-apoptotic factors. Importantly, blocking autophagy in infected PMN partially restored levels of apoptosis to that of uninfected PMN, suggesting a connection between the autophagic and apoptotic pathways during intracellular survival. These results provide a novel mechanism for intracellular survival and suggest that may be subverting crosstalk between the autophagic and apoptosis pathways in order to maintain an intracellular niche within human PMN.