Bacterial infectious diseases can lead to death or serious illnesses. Among major bacterial virulence factors are pore-forming toxins (PFTs) which will damage the plasma membrane of host cells, i.e. immune cells, epithelial and endothelial cells. PFTs were shown to be expressed during infection and target immune cells which are central players in host defense. Immune cells respond to PFTs attack by activating membrane repair mechanisms, intracellular signaling pathways, phagocytosis, cytokine production, and programmed cell death mechanisms. In addition, the direct effects of PFTs on signaling pathway induction or PFT-induced epithelial/endothelial cell damage and subsequent release of cytokines will activate and recruit immune cells, thereby initiating and regulating inflammatory processes, which may culminate in massive tissue destruction.
At the single-cell level, the assembly of PFTs leads to deleterious pores in the plasma membrane of immune cells, permeabilization, and ion influx and/or outflow (i.e. calcium or potassium). Cells can repair these harmful pores through cellular repair mechanisms that involve isolating the damaged membrane sites and expelling them in the form of microvesicles, endocytosis of damaged membrane areas, and isolation of damaged membrane sites by blistering. These repair mechanisms must act quickly because prolonged cellular ion homeostasis imbalance (i.e., high calcium levels) can also lead to the induction of programmed cell death, ER stress, UPR, and activation of stress response MAPK pathways.
Depending on the immune cell type, cellular resistance to PFTs can be traced back to the identity of the PFT and the effectiveness of membrane repair mechanisms. However, essential factors or pathways of the cellular membrane repair machinery in immune cells have yet to be identified. The deleterious effects of PFTs, i. e. cytolysis or cell death, also depend on the concentration of PFT that hits the host cell. Low concentrations of PFTs can induce various cellular responses, i.e. activation and/or changes in immune cell phenotypes that can facilitate or weaken an appropriate immune response.
In this Research Topic, we welcome the submission of Original Research, Review, Mini Review, Perspective, and General Commentary articles covering, but not limited to, the following subtopics:
• Mechanisms of pro- or anti-inflammatory responses to PFTs
• Updates on the molecular mechanisms of PTFs on host cells
• Updates on the mechanisms of immune cell response to PFTs
• Updates on the role of PFTs in infectious disease pathogenesis
• Mechanisms of cellular resistance to PFTs
• Effect of concentration of PTFs on host cell response
Bacterial infectious diseases can lead to death or serious illnesses. Among major bacterial virulence factors are pore-forming toxins (PFTs) which will damage the plasma membrane of host cells, i.e. immune cells, epithelial and endothelial cells. PFTs were shown to be expressed during infection and target immune cells which are central players in host defense. Immune cells respond to PFTs attack by activating membrane repair mechanisms, intracellular signaling pathways, phagocytosis, cytokine production, and programmed cell death mechanisms. In addition, the direct effects of PFTs on signaling pathway induction or PFT-induced epithelial/endothelial cell damage and subsequent release of cytokines will activate and recruit immune cells, thereby initiating and regulating inflammatory processes, which may culminate in massive tissue destruction.
At the single-cell level, the assembly of PFTs leads to deleterious pores in the plasma membrane of immune cells, permeabilization, and ion influx and/or outflow (i.e. calcium or potassium). Cells can repair these harmful pores through cellular repair mechanisms that involve isolating the damaged membrane sites and expelling them in the form of microvesicles, endocytosis of damaged membrane areas, and isolation of damaged membrane sites by blistering. These repair mechanisms must act quickly because prolonged cellular ion homeostasis imbalance (i.e., high calcium levels) can also lead to the induction of programmed cell death, ER stress, UPR, and activation of stress response MAPK pathways.
Depending on the immune cell type, cellular resistance to PFTs can be traced back to the identity of the PFT and the effectiveness of membrane repair mechanisms. However, essential factors or pathways of the cellular membrane repair machinery in immune cells have yet to be identified. The deleterious effects of PFTs, i. e. cytolysis or cell death, also depend on the concentration of PFT that hits the host cell. Low concentrations of PFTs can induce various cellular responses, i.e. activation and/or changes in immune cell phenotypes that can facilitate or weaken an appropriate immune response.
In this Research Topic, we welcome the submission of Original Research, Review, Mini Review, Perspective, and General Commentary articles covering, but not limited to, the following subtopics:
• Mechanisms of pro- or anti-inflammatory responses to PFTs
• Updates on the molecular mechanisms of PTFs on host cells
• Updates on the mechanisms of immune cell response to PFTs
• Updates on the role of PFTs in infectious disease pathogenesis
• Mechanisms of cellular resistance to PFTs
• Effect of concentration of PTFs on host cell response
