PITing host against bacteria in the fight for infection control

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Science Translational Medicine  14 Sep 2016:
Vol. 8, Issue 356, pp. 356ec148
DOI: 10.1126/scitranslmed.aah7021

The human innate immune system has evolved to recognize invading organisms and clear them away. In parallel, bacteria have evolved to evade these host defense mechanisms to persist and replicate. Jorgensen et al. further characterize this evolutionary arms race in their new study reporting that infected immune cells hold bacteria hostage in a specialized membrane pore during a programmed explosion, immobilizing them until backup arrives to clear away the damage.

The highly conserved inflammasome complex senses intracellular bacteria and incites a proinflammatory response that induces pyroptosis, an inflammatory, lytic programmed cell death. Pyroptosis protects the host cell to prevent further bacterial replication in the intracellular niche. Jorgensen and colleagues used a combination of live cell microscopy and genetic manipulation of the pyroptosis machinery to reveal that membrane pores, termed pore-induced cellular traps (PITs), form around bacteria during pyroptotic cell lysis. Although similar to neutrophil extracellular traps (NETs), PITs do not directly kill invading pathogens but rather sequester them to prevent the spread of infection. Neutrophils, recruited by “find me” and “eat me” signals displayed on the PIT, engulf both the pathogen and the dead infected cell to execute bacterial killing. This mechanism allows the host to execute two critical tasks to clear the infection—kill the bacteria and clear away dead cell debris to restore tissue homeostasis—in one step.

This understanding of host bacterial trapping mechanisms could be important as the emergence of antibiotic-resistant bacteria threatens to become a global epidemic. Harnessing the power of nonspecific machinery used by the host cells to successfully fend off infection could minimize the need for specifically targeting constantly adapting pathogens to block infections. These concepts could therefore open entirely new approaches for the treatment of infectious diseases and combat a global health concern on the horizon.

I. Jorgensenet al., Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J. Exp. Med. 10.1084/jem.20151613 (2016). [Abstract]

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