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Inflammasome Regulation in Macrophages by Streptococcus pyogenes

Westerlund, Elsa (2013) MOBM14 20131
Degree Projects in Molecular Biology
Abstract
Popular science summary:

NADase – a way to avoid immune system activation?

Streptococcus pyogenes (S. pyogenes) are bacteria that cause many different kinds of diseases in humans, for example strep throat, scarlet fever and necrotizing fasciitis, the ”flesh-eating disease”. An infection with this type of bacteria can also lead to heart and kidney damage, thought to be caused by our immune system mistaking structures in our own body for structures on the bacteria, an autoimmune attack.

Diseause-causing bacteria use virulence factors to promote infection and spread. These virulence factors can be used to attach to human cells and to avoid being ingested and killed by our immune cells, among many other things. Two examples of S.... (More)
Popular science summary:

NADase – a way to avoid immune system activation?

Streptococcus pyogenes (S. pyogenes) are bacteria that cause many different kinds of diseases in humans, for example strep throat, scarlet fever and necrotizing fasciitis, the ”flesh-eating disease”. An infection with this type of bacteria can also lead to heart and kidney damage, thought to be caused by our immune system mistaking structures in our own body for structures on the bacteria, an autoimmune attack.

Diseause-causing bacteria use virulence factors to promote infection and spread. These virulence factors can be used to attach to human cells and to avoid being ingested and killed by our immune cells, among many other things. Two examples of S. pyogenes virulence factors are SLO and NADase. SLO can form a pore in cells and is needed to transport NADase into cells, but it is not known exactly how this works. When it gets inside, NADase can split a molecule called NAD+ into two parts, called nicotinamide and ADP-ribose. Nicotinamide has anti-inflammatory effects, while ADP-ribose has opposite effects.

I have looked at the ways NADase and SLO affect a type of immune cell called a macrophage. Macrophages are part of the innate immune system, the second line of defense against invading agents (the first is our skin) and kill bacteria and viruses by ingesting (eating) them in a process called phagocytosis. A sensor of danger and infection called the the inflammasome is used by macrophages and other immune cells to detect for example invading bacteria,

Activation of the inflammasome leads to release of a cytokine called IL-1β (Figure 1). Cytokines are signaling molecules and can be seen as a way for the immune cells to communicate with each other. In our case IL-1β is used by macrophages to say that the body is under attack.

During my project I showed that streptococci without NADase caused more release of IL-1β than bacteria with it, which could mean that NADase prevents inflammasome activation. This prevention could be due to the anti-inflammatory effects of nicotinamide, since adding nicotinamide to cells before infecting them with streptococci resulted in a decrease in IL-1β production. I also observed that bacteria without SLO or NADase were present inside macrophages to a higher degree than bacteria with these virulence factors, which could mean that they prevent phagocytosis.

These results imply that the effects of NADase and SLO together could be a way for the bacteria to avoid activating the immune system, so that they are able to spread undetected in the body.


Supervisor: Jenny Persson
Master’s degree project 30 credits in Cellular and Molecular Immunology 2013
Department of Biology, Lund University
Section of Immunology, Department of Medicine (Less)
Please use this url to cite or link to this publication:
author
Westerlund, Elsa
supervisor
organization
course
MOBM14 20131
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
4054055
date added to LUP
2013-09-19 13:53:55
date last changed
2013-09-19 13:53:55
@misc{4054055,
  abstract     = {Popular science summary:

NADase – a way to avoid immune system activation?

Streptococcus pyogenes (S. pyogenes) are bacteria that cause many different kinds of diseases in humans, for example strep throat, scarlet fever and necrotizing fasciitis, the ”flesh-eating disease”. An infection with this type of bacteria can also lead to heart and kidney damage, thought to be caused by our immune system mistaking structures in our own body for structures on the bacteria, an autoimmune attack.

Diseause-causing bacteria use virulence factors to promote infection and spread. These virulence factors can be used to attach to human cells and to avoid being ingested and killed by our immune cells, among many other things. Two examples of S. pyogenes virulence factors are SLO and NADase. SLO can form a pore in cells and is needed to transport NADase into cells, but it is not known exactly how this works. When it gets inside, NADase can split a molecule called NAD+ into two parts, called nicotinamide and ADP-ribose. Nicotinamide has anti-inflammatory effects, while ADP-ribose has opposite effects.

I have looked at the ways NADase and SLO affect a type of immune cell called a macrophage. Macrophages are part of the innate immune system, the second line of defense against invading agents (the first is our skin) and kill bacteria and viruses by ingesting (eating) them in a process called phagocytosis. A sensor of danger and infection called the the inflammasome is used by macrophages and other immune cells to detect for example invading bacteria,

Activation of the inflammasome leads to release of a cytokine called IL-1β (Figure 1). Cytokines are signaling molecules and can be seen as a way for the immune cells to communicate with each other. In our case IL-1β is used by macrophages to say that the body is under attack.

During my project I showed that streptococci without NADase caused more release of IL-1β than bacteria with it, which could mean that NADase prevents inflammasome activation. This prevention could be due to the anti-inflammatory effects of nicotinamide, since adding nicotinamide to cells before infecting them with streptococci resulted in a decrease in IL-1β production. I also observed that bacteria without SLO or NADase were present inside macrophages to a higher degree than bacteria with these virulence factors, which could mean that they prevent phagocytosis.

These results imply that the effects of NADase and SLO together could be a way for the bacteria to avoid activating the immune system, so that they are able to spread undetected in the body.


Supervisor: Jenny Persson
Master’s degree project 30 credits in Cellular and Molecular Immunology 2013
Department of Biology, Lund University
Section of Immunology, Department of Medicine},
  author       = {Westerlund, Elsa},
  language     = {eng},
  note         = {Student Paper},
  title        = {Inflammasome Regulation in Macrophages by Streptococcus pyogenes},
  year         = {2013},
}