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Mycobacterial regulation of macrophage responses to infection : Induction and functional role of type I interferon

Nobs, Esther LU (2024)
Abstract
Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The... (More)
Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The specialized protein secretion system ESX-1 is required for full virulence of mycobacteria and is involved in evasion strategies such as phagosomal escape and induction of type I interferons. The role of type I interferons in mycobacterial infection remains incompletely understood, although evidence strongly suggests a host detrimental role. The work presented in this thesis brings light on these key events during mycobacterial infection and contributes with new insights regarding the onset and functional role of the type I interferon response during infection. (Less)
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author
supervisor
opponent
  • Professor Rottenberg, Martin, Karolinska institutet, Institutionen för mikrobiologi, tumör-och cellbiologi
organization
publishing date
type
Thesis
publication status
published
subject
keywords
infection, macrophage, mycobacteria, ESX-1, membrane permeabilization, type I interferon
pages
167 pages
publisher
Lund University, Faculty of Science
defense location
The Blue Hall, Department of Biology, Sölvegatan 37, Lund.
defense date
2024-06-04 09:00:00
ISBN
978-91-8039-952-4
978-91-8039-953-4
language
English
LU publication?
yes
id
8c075484-7345-48b4-a751-f7cb7b1802df
date added to LUP
2024-05-03 11:17:40
date last changed
2024-05-13 07:43:08
@phdthesis{8c075484-7345-48b4-a751-f7cb7b1802df,
  abstract     = {{Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The specialized protein secretion system ESX-1 is required for full virulence of mycobacteria and is involved in evasion strategies such as phagosomal escape and induction of type I interferons. The role of type I interferons in mycobacterial infection remains incompletely understood, although evidence strongly suggests a host detrimental role. The work presented in this thesis brings light on these key events during mycobacterial infection and contributes with new insights regarding the onset and functional role of the type I interferon response during infection.}},
  author       = {{Nobs, Esther}},
  isbn         = {{978-91-8039-952-4}},
  keywords     = {{infection; macrophage; mycobacteria; ESX-1; membrane permeabilization; type I interferon}},
  language     = {{eng}},
  publisher    = {{Lund University, Faculty of Science}},
  school       = {{Lund University}},
  title        = {{Mycobacterial regulation of macrophage responses to infection : Induction and functional role of type I interferon}},
  url          = {{https://lup.lub.lu.se/search/files/182402864/Esther_Nobs_-_WEBB.pdf}},
  year         = {{2024}},
}