Microbe-induced apoptosis in phagocytic cells and its role in innate immunity

Apoptosis, or programmed cell death, is a controlled process by which aged or damages cells are eliminated in multicellular organisms. Neutrophils, short-lived phagocytes of the innate immune system, are highly equipped effectors that can sense, locate, ingest and kill bacterial pathogens. Inflammatory mediators and the presence of bacterial products at the foci of infection regulate the function and life span of these cells. Modulation of neutrophil apoptosis and the subsequent clearance by scavenger cells, such as macrophages, is part of a balanced inflammatory process leading to resolution of inflammation. Many pathogens are capable of modulating host cell apoptosis, and thereby influence the progression of disease. Hence, this thesis was aiming at elucidating mechanisms involved in pathogen- and host-modulated apoptosis and its contribution to the inflammatory process.We found that different routes of bacterial entry, i.e. through invasion or by receptor-mediated phagocytosis, triggered different signaling pathways within phagocytes. Invasion of virulent Salmonella caused apoptosis, a process requiring activation of the Rho GTPases Rac1 and Cdc42. On the other hand, phagocytosis of the non-invasive Salmonella inhibited apoptosis despite similar intracellular survival as the invasive bacteria. Protection against phagocytosis-induced apoptosis was regulated by tyrosine- and PI3-kinase-dependent activation of AKT (also called PKB for protein kinase B). Furthermore, inhibiting the intraphagosomal production of reactive oxygen species (ROS) in neutrophils during phagocytosis…


Immediate response to infection
Adhesion and migration
Phagocytosis and intracellular killing
Neutrophils and inflammation
Elimination of neutrophils
Morphology of apoptosis
Bcl-2 family
Initiation of apoptosis
Regulation of apoptosis
Apoptosis in neutrophils
Apoptosis modulation by microbes
Type-ІІІ secretion system
Clearance of apoptotic cells
Cell surface changes and recognition
Cofactors for recognition
Consequences of apoptotic cells clearance
Aim of the dissertation
Results & Discussion
Invasion and pro-apoptotic signaling in phagocytes (paper Ι and ΙΙ)
Phagocytosis and anti-apoptotic signaling in phagocytes (paper Ι and ΙΙ)
Role for lysosomes (azurophilic granules) in neutrophil apoptosis (paper ΙΙΙ)
Modulation of macrophage activation by apoptotic neutrophils (paper ІV)

Author: Blomgran, Robert

Source: Linköping University

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