Phagocytosis by neutrophils - studies on phagosome dynamics and membrane traffic modulation by Streptococcus pyogenes

Author

Summary, in English

Neutrophils are our most numerous and deadly white blood cells and without them we would succumb quickly

to infections by pathogens. The main mechanism that the neutrophils employ for our protection is

phagocytosis, where they eat and enclose their target inside a membrane-bound organelle, the phagosome.

Neutrophil phagosomes are highly dynamic entities, and a large amount of antimicrobial substances are

released to their interior within seconds of formation. In most cases this will kill the engulfed microbe, but

there are exceptions. Streptococcus pyogenes is one of our most common pathogens and is responsible for a

wide range of diseases. Recently it has been demonstrated that these bacteria are able to survive phagocytosis by

neutrophils. This doctoral thesis is about explaining those mechanisms.

What is described in this thesis is the development of new methods for studying phagosome biogenesis and

maturation, including creating magnetic bacteria to isolate phagosomes and advanced microscopy for live

measurements of phagosomal pH. The employment of cell lines and their differentiation into neutrophils is

shown to be a useful research tool. Using these methods, novel findings regarding mechanisms for fusion

between neutrophil granules and phagosomes are demonstrated. It is shown that S. pyogenes interfere with the

intracellular membrane traffic of neutrophils, leading to a decreased delivery of antimicrobial substances and

impaired acidification of S. pyogenes-containing phagosomes, helping them to survive phagocytosis.

Topic

  • Infectious Medicine

Keywords

  • fluorescence microscopy
  • membrane traffic
  • neutrophil
  • Streptococcus pyogenes
  • phagosome
  • phagocytosis

Status

Published

Supervisor

ISBN/ISSN/Other

  • ISSN: 1652-8220
  • ISBN: 978-91-86443-58-0

Defence date

7 May 2010

Defence time

09:00

Defence place

GK-salen, BMC, Lund