Further Insight into the Mechanism of Human PMN Lysis following Phagocytosis of Staphylococcus aureus

Rungelrath, Viktoria; Porter, Adeline R.; Małachowa, Natalia; Freedman, Brett A.; Leung, Jacqueline M.; Voyich, Jovanka M.; Otto, Michael; Kobayashi, Scott D.; DeLeo, Frank R.

doi:10.1128/spectrum.00888-21

Cited by 3 publications

(5 citation statements)

References 69 publications

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“…Consistent with this notion, USA300 isogenic mutant strains lacking genes encoding PVL retain full capacity to cause lysis after phagocytosis 231 . In contrast, S. aureus isogenic mutant strains lacking genes encoding LukGH/AB, PSMs, or Hla have significantly reduced ability to cause neutrophil lysis after phagocytosis 232‐236 . At present, it is not clear how these cytolytic toxins contribute to cytolysis caused by ingested S. aureus .…”

Section: Neutrophil Lysis (Cytolysis)mentioning

confidence: 98%

“…231 In contrast, S. aureus isogenic mutant strains lacking genes encoding LukGH/ AB, PSMs, or Hla have significantly reduced ability to cause neutrophil lysis after phagocytosis. [232][233][234][235][236] At present, it is not clear how these cytolytic toxins contribute to cytolysis caused by ingested S. This vaccine approach has worked relatively well in animal infection models, and human clinical trials are in progress.…”

Section: Contribution Of S Aureus Molecules To Pmn Lysis After Phagoc...mentioning

confidence: 99%

“…At present, it is not clear how these cytolytic toxins contribute to cytolysis caused by ingested S. aureus . Recent studies by Rungelrath et al 236 demonstrated that USA300 is retained in intact phagosomes until the point of PMN lysis. Therefore, this cytolytic process does not requires escape of S. aureus from the phagosome.…”

Section: Neutrophil Lysis (Cytolysis)mentioning

confidence: 99%

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Microbes and the fate of neutrophils

Kobayashi

DeLeo

Quinn

2022

Immunological Reviews

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Summary Neutrophils or polymorphonuclear neutrophils (PMNs) are an important component of innate host defense. These phagocytic leukocytes are recruited to infected tissues and kill invading microbes. There are several general characteristics of neutrophils that make them highly effective as antimicrobial cells. First, there is tremendous daily production and turnover of granulocytes in healthy adults—typically 1011 per day. The vast majority (~95%) of these cells are neutrophils. In addition, neutrophils are mobilized rapidly in response to chemotactic factors and are among the first leukocytes recruited to infected tissues. Most notably, neutrophils contain and/or produce an abundance of antimicrobial molecules. Many of these antimicrobial molecules are toxic to host cells and can destroy host tissues. Thus, neutrophil activation and turnover are highly regulated processes. To that end, aged neutrophils undergo apoptosis constitutively, a process that contains antimicrobial function and proinflammatory capacity. Importantly, apoptosis facilitates nonphlogistic turnover of neutrophils and removal by macrophages. This homeostatic process is altered by interaction with microbes and their products, as well as host proinflammatory molecules. Microbial pathogens can delay neutrophil apoptosis, accelerate apoptosis following phagocytosis, or cause neutrophil cytolysis. Here, we review these processes and provide perspective on recent studies that have potential to impact this paradigm.

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Section: Neutrophil Lysis (Cytolysis)mentioning

confidence: 98%

Section: Contribution Of S Aureus Molecules To Pmn Lysis After Phagoc...mentioning

confidence: 99%

Section: Neutrophil Lysis (Cytolysis)mentioning

confidence: 99%

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Microbes and the fate of neutrophils

Kobayashi

DeLeo

Quinn

2022

Immunological Reviews

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“…Although most internalized bacteria are killed, a fraction resist killing and use the phagocytes to mediate dissemination to other sites. For S. aureus specifically, intracellular survival helps the bacteria evade innate immune defenses and destroy neutrophils by programmed necrosis (135), with leukocidins mediating bacterial survival/escape through induction of programmed necrosis (136). Moreover, many viruses perform membrane fusion events required for entry into host cells in the low-pH endosome (e.g., influenza and Ebola).…”

Section: Antibody-antibiotic Conjugates Targeting Internalized Bacteriamentioning

confidence: 99%

Outsmarting Pathogens with Antibody Engineering

Qerqez

Silva

Maynard

2023

Annual Review of Chemical and Biomolecular Engineering

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There is growing interest in identifying antibodies that protect against infectious diseases, especially for high-risk individuals and pathogens for which no vaccine is yet available. However, pathogens that manifest as opportunistic or latent infections express complex arrays of virulence-associated proteins and are adept at avoiding immune responses. Some pathogens have developed strategies to selectively destroy antibodies, whereas others create decoy epitopes that trick the host immune system into generating antibodies that are at best nonprotective and at worst enhance pathogenesis. Antibody engineering strategies can thwart these efforts by accessing conserved neutralizing epitopes, generating Fc domains that resist capture or degradation and even accessing pathogens hidden inside cells. Design of pathogen-resistant antibodies can enhance protection and guide development of vaccine immunogens against these complex pathogens. Here, we discuss general strategies for design of antibodies resistant to specific pathogen defense mechanisms. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 14 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…10 Furthermore, under optimal conditions, activation prompts neutrophils to engage transcriptional pathways that trigger apoptosis and initiate events that culminate in termination of the inflammatory response. [23][24][25] Sometimes, as with interactions with particular bacteria, such as Staphylococcus aureus, or when stimulation is excessive, neutrophils undergo a necrotic cell death 24,26 and thereby release cytoplasmic contents that provide danger signals to drive additional inflammation. In some settings, neutrophils, as well as other cells, release extracellular traps (aka ETs), whose DNA may entrap microbes, contribute to autoimmune disease, or promote further inflammation.…”

Section: The S Truc Ture Comp Os Iti On and B I Ology Of H Uman Neu...mentioning

confidence: 99%

Human neutrophils ≠ murine neutrophils: Does it matter?

Nauseef

2022

Immunological Reviews

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Our understanding of many of the biological processes related to human health and disease derives in large part from two investigative approaches, namely clinical observations of patients afflicted with disease, either acquired or inherited, and animal experimental systems intended to model human disorders. Astute clinicians in search of alleviating the suffering of their patients drive basic and translational studies to identify underlying physiology, both normal and aberrant. Particularly powerful because of extensive background genetic information and well-characterized inbred strains, murine experimental systems have served to model a wide spectrum of human diseases, including infections, autoimmune disorders, inflammatory syndromes, and malignancies. Investigators often use murine experimental systems to assess the role of neutrophils in a specific disease, syndrome, or malignancy, either as their exclusive

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Further Insight into the Mechanism of Human PMN Lysis following Phagocytosis of Staphylococcus aureus

Abstract: S. aureus strain USA300 has the ability to cause rapid lysis of human neutrophils after phagocytosis. Although this phenomenon likely contributes to the success of USA300 as a human pathogen, our knowledge of the mechanism remains incomplete.

Cited by 3 publications

References 69 publications

Microbes and the fate of neutrophils

Microbes and the fate of neutrophils

Outsmarting Pathogens with Antibody Engineering

Human neutrophils ≠ murine neutrophils: Does it matter?

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