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.
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.
Department/s
Publishing year
2010
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2010:43
Full text
- Available as PDF - 25 MB
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Document type
Dissertation
Publisher
Lund University
Topic
- Infectious Medicine
Keywords
- fluorescence microscopy
- membrane traffic
- neutrophil
- Streptococcus pyogenes
- phagosome
- phagocytosis
Status
Published
Supervisor
- Hans Tapper
- Lars Björck
- Sergio Grinstein
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
Opponent
- Joel Swanson (Prof)