The role of mitochondrial ROS in antibacterial immunity

Пинегин, Б В; Vorobjeva, N.V.; Pashenkov, Мikhail; Chernyak, Boris V.

doi:10.1002/jcp.26117

Cited by 79 publications

(49 citation statements)

References 94 publications

(137 reference statements)

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“…mtROS have also been increasingly reported to contribute to both innate and adaptive immunity [34, 50], and increased production of mitochondria-derived species likely explains the Pam2-ODN-increased superoxide we detect [23].…”

Section: Discussionmentioning

confidence: 99%

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

et al. 2019

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Pneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs’ mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against a bacterial pathogen and provide mechanistic insights into means to protect vulnerable patients against lethal infections.

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Section: Discussionmentioning

confidence: 99%

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

et al. 2019

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“…Mitochondria can also act as an ROS‐producing organelle . This mechanism has been shown to play a role in host defense from pathogens by macrophages .…”

Section: Functional Diversity In Phagocytic Cellsmentioning

confidence: 99%

Diversity and environmental adaptation of phagocytic cell metabolism

Rice

McVicar

Weiss

2018

Journal of Leukocyte Biology

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Phagocytes are cells of the immune system that play important roles in phagocytosis, respiratory burst and degranulation-key components of innate immunity and response to infection. This diverse group of cells includes monocytes, macrophages, dendritic cells, neutrophils, eosinophils, and basophils-heterogeneous cell populations possessing cell and tissue-specific functions of which cellular metabolism comprises a critical underpinning. Core functions of phagocytic cells are diverse and sensitive to alterations in environmental- and tissue-specific nutrients and growth factors. As phagocytic cells adapt to these extracellular cues, cellular processes are altered and may contribute to pathogenesis. The considerable degree of functional heterogeneity among monocyte, neutrophil, and other phagocytic cell populations necessitates diverse metabolism. As we review our current understanding of metabolism in phagocytic cells, gaps are focused on to highlight the need for additional studies that hopefully enable improved cell-based strategies for counteracting cancer and other diseases.

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“…For a long time, it was believed that mitochondria do not play a significant role in the functioning of neutrophils, since their content in these cells is low, energy supply is supported by glycolysis, and NADPH oxidase is the main source of ROS. Subsequently, however, it turned out that mitochondria are involved in the transmission of signals that determine main responses of the neutrophils to pathogens [ 14 ]. It was found that mitochondrial ROS are involved in the activation of NADPH oxidase and in the induction of NETosis caused by various stimuli [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

NETosis: Molecular Mechanisms, Role in Physiology and Pathology

Vorobjeva

Chernyak

2020

Biochemistry Moscow

295

227

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NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis. Induction of NETosis depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Activation of NADPH oxidase depends on increase in the concentration of Ca 2+ in the cytoplasm and in some cases on the generation of ROS in mitochondria. NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane. In this review, basic mechanisms of NETosis, as well as its role in the pathogenesis of some diseases including COVID-19 are discussed.

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The role of mitochondrial ROS in antibacterial immunity

Cited by 79 publications

References 94 publications

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

Diversity and environmental adaptation of phagocytic cell metabolism

NETosis: Molecular Mechanisms, Role in Physiology and Pathology

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