Venizelos Papayannopoulos group

Mechanisms of neutrophil-mediated immune defense

Multicellular organisms evolved sophisticated immune systems to protect themselves against infection. We are interested in understanding how our immune system regulates its responses to microbial challenges. We focus on neutrophils, since these phagocytes play central microbicidal and regulatory roles during the course of infection.

Neutrophils are among the first immune cells recruited to sites of infection, undertaking several strategies to eliminate the invading agents. They engulf and kill microbes intracellularly and release antimicrobial factors that combat pathogens extracellularly through degranulation and the release of neutrophil extracellular traps (NETs).

NET formation

NETs are composed of decondensed chromatin and antimicrobial proteins and form web-like structures that trap and kill bacteria, fungi and parasites. Although the specific role of NETs during infection is still becoming apparent, they are implicated in immune defense and autoimmune disease. It is therefore important to unveil the mechanisms that regulate NET release.

Neutrophils release NETs through a novel cell death mechanism involving some fascinating cell biology. During NET formation the nuclear envelop disassembles and the chromatin decondenses to mix with neutrophil antimicrobial factors while the cell remains intact.

At the molecular level, reactive oxygen species trigger the selective translocation of a neutrophil specific protease, Neutrophil elastase, to the nucleus where histones are partially cleaved to promote chromatin decondensation.

We are studying the mechanism of Neutrophil elastase translocation and we are particularly interested in reactive oxygen signaling during this process. We are also trying to understand the nature of the upstream signals governing NET release.

Papayannopoulos group

Dr Venizelos Papayannopoulos

Venizelos Papayannopoulos
vpapaya@nimr.mrc.ac.uk

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