Inhibition of Fibroblast Apoptosis by Borrrelia afzelii, Coxiella burnetii and Bartonella henselae

Apoptosis is a genetically controlled mechanism of cell death involved in the regulation of tissue homeostasis. The aim of this study was to investigate the influence of Borrelia afzelii, Coxiella burnetii, and Bartonella henselae bacteria on apoptosis measured as the level of caspase 3 activity in human fibroblast cells HEL-299. Our findings show that C. burnetii bacteria may inhibit the process of apoptosis in the host cells for a long time. This can permit intracellular survival in the host and mediatingthe development of chronic disease.

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Inhibition of Autophagy by 3-Methyladenine restricts Murine Cytomegalo virus Replication

10.21203/rs.3.rs-39753/v1 ◽

2020 ◽

Author(s):

Xinyan Zhang ◽

Linlin Zhang ◽

Yidan Bi ◽

Ting Xi ◽

Zhan Zhang ◽

...

Keyword(s):

Cell Death ◽

Virus Replication ◽

Post Infection ◽

Caspase 3 ◽

Plaque Assay ◽

Virus Titer ◽

Kinase Domain ◽

Host Cells ◽

Mcmv Infection ◽

Related Factors

Abstract Background:Cytomegalovirus (CMV) could induce autophagy early upon infection, which might have an impact on virus replication and the survival of host cells. The purpose ofthe present study was to determine how autophagy effects virus replication and whether it is associated with caspase-3 dependent apoptosis duringmurine cytomegalovirus (MCMV) infection. Methods:The eyecup isolated from adultC57BL/6J mice (6-8 weeks old) and mouse embryo fibroblast cells (MEFs) were cultured and infected with MCMV K181 strain, following by treated with 3-methyladenine (3-MA)or rapamycin to block or activate autophagy.Immunofluorescence staining and western blot were used to detect the expression of early antigen (EA) of MCMV, autophagy and cell death related factors. Plaque assay was performed to detect the virus titer in different groups. TUNEL assay was used to measure the percentage of cell death.Results: Results showed that autophagy was induced at 24,72 and 96hours post infection (hpi)with MCMV in MEFs. In the eyecup culture, it also showed that autophagy was induced at 4 and 7days post infection (dpi).In addition, caspase-3 dependent apoptosis and receptor-interacting kinase 1/ receptor-interacting kinase 3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) dependent necroptosis were induced by MCMV infection in eyecup.In MEFs, caspase-3 dependent apoptosis was inhibited, whileRIPK1/RIPK3/MLKL dependent necroptosis was activated with MCMV infection. Once treatment with 3-MA, there were significantly less active virus particles released in MEFs and eyecup, also EA expression was significantly inhibited in the eyecup. However, treatment with rapamycin have no such significant influence on either virus titer or EA expression in MEFs and eyecup. Furthermore, cleaved caspase-3 was elevated, while RIPK1/RIPK3/MLKL pathway was inhibited with treatment of 3-MA both in MEFs and eyecup. Conclusion:Inhibition of autophagy by 3-MA could both restrict virus replication and promote caspase-3 dependent apoptosis in the eyecup and MEFs with MCMV infection.It can be explained that on the early periodof MCMV infection, suppressed autophagy process directly reduced virus release.Thereafter, caspase-3 dependent apoptosis was activated and resulted in decreased virus replication.

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Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria

Infection and Immunity ◽

10.1128/iai.00863-07 ◽

2007 ◽

Vol 75 (11) ◽

pp. 5282-5289 ◽

Cited By ~ 65

Author(s):

Anja Lührmann ◽

Craig R. Roy

Keyword(s):

Cell Death ◽

Host Cell ◽

Coxiella Burnetii ◽

Mammalian Cells ◽

Q Fever ◽

Host Cells ◽

Intracellular Pathogen ◽

Obligate Intracellular ◽

Cell Death Pathway ◽

Obligate Intracellular Pathogen

ABSTRACT Coxiella burnetii is an obligate intracellular pathogen and the etiological agent of the human disease Q fever. C. burnetii infects mammalian cells and then remodels the membrane-bound compartment in which it resides into a unique lysosome-derived organelle that supports bacterial multiplication. To gain insight into the mechanisms by which C. burnetii is able to multiply intracellularly, we examined the ability of host cells to respond to signals that normally induce apoptosis. Our data show that mammalian cells infected with C. burnetii are resistant to apoptosis induced by staurosporine and UV light. C. burnetii infection prevented caspase 3/7 activation and limited fragmentation of the host cell nucleus in response to agonists that induce apoptosis. Inhibition of bacterial protein synthesis reduced the antiapoptotic effect that C. burnetii exerted on infected host cells. Inhibition of apoptosis in C. burnetii-infected cells did not correlate with the degradation of proapoptotic BH3-only proteins involved in activation of the intrinsic cell death pathway; however, cytochrome c release from mitochondria was diminished in cells infected with C. burnetii upon induction of apoptosis. These data indicate that C. burnetii can interfere with the intrinsic cell death pathway during infection by producing proteins that either directly or indirectly prevent release of cytochrome c from mitochondria. It is likely that inhibition of apoptosis by C. burnetii represents an important virulence property that allows this obligate intracellular pathogen to maintain host cell viability despite inducing stress that would normally activate the intrinsic death pathway.

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Phenotype of a Herpes Simplex Virus Type 1 Mutant That Fails To Express Immediate-Early Regulatory Protein ICP0

Journal of Virology ◽

10.1128/jvi.78.4.1763-1774.2004 ◽

2004 ◽

Vol 78 (4) ◽

pp. 1763-1774 ◽

Cited By ~ 95

Author(s):

Roger D. Everett ◽

Chris Boutell ◽

Anne Orr

Keyword(s):

Cell Death ◽

High Probability ◽

Human Fibroblasts ◽

Regulatory Protein ◽

Fibroblast Cells ◽

Human Fibroblast Cells ◽

Infected Cells ◽

Protein Icp0 ◽

Simplex Virus

ABSTRACT Herpes simplex virus type 1 (HSV-1) immediate-early (IE) regulatory protein ICP0 is required for efficient progression of infected cells into productive lytic infection, especially in low-multiplicity infections of limited-passage human fibroblasts. We have used single-cell-based assays that allow detailed analysis of the ICP0-null phenotype in low-multiplicity infections of restrictive cell types. The major conclusions are as follows: (i) there is a threshold input multiplicity above which the mutant virus replicates normally; (ii) individual cells infected below the threshold multiplicity have a high probability of establishing a nonproductive infection; (iii) such nonproductively infected cells have a high probability of expressing IE products at 6 h postinfection; (iv) even at 24 h postinfection, IE protein-positive nonproductively infected human fibroblast cells exceed the number of cells that lead to plaque formation by up to 2 orders of magnitude; (v) expression of individual IE proteins in a proportion of the nonproductively infected cells is incompletely coordinated; (vi) the nonproductive cells can also express early gene products at low frequencies and in a stochastic manner; and (vii) significant numbers of human fibroblast cells infected at low multiplicity by an ICP0-deficient virus are lost through cell death. We propose that in the absence of ICP0 expression, HSV-1 infected human fibroblasts can undergo a great variety of fates, including quiescence, stalled infection at a variety of different stages, cell death, and, for a minor population, initiation of formation of a plaque.

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Management of cell death in parasitic infections

Seminars in Immunopathology ◽

10.1007/s00281-021-00875-8 ◽

2021 ◽

Author(s):

Lidia Bosurgi ◽

Carla V. Rothlin

Keyword(s):

Cell Death ◽

Parasitic Infection ◽

Host Cells ◽

Parasitic Infections ◽

Helminth Parasites ◽

Cellular Regulation ◽

Helminth Infections ◽

Host Cell Death ◽

Long Time

AbstractFor a long time, host cell death during parasitic infection has been considered a reflection of tissue damage, and often associated with disease pathogenesis. However, during their evolution, protozoan and helminth parasites have developed strategies to interfere with cell death so as to spread and survive in the infected host, thereby ascribing a more intriguing role to infection-associated cell death. In this review, we examine the mechanisms used by intracellular and extracellular parasites to respectively inhibit or trigger programmed cell death. We further dissect the role of the prototypical “eat-me signal” phosphatidylserine (PtdSer) which, by being exposed on the cell surface of damaged host cells as well as on some viable parasites via a process of apoptotic mimicry, leads to their recognition and up-take by the neighboring phagocytes. Although barely dissected so far, the engagement of different PtdSer receptors on macrophages, by shaping the host immune response, affects the overall infection outcome in models of both protozoan and helminth infections. In this scenario, further understanding of the molecular and cellular regulation of the PtdSer exposing cell-macrophage interaction might allow the identification of new therapeutic targets for the management of parasitic infection.

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Ionizing Radiation-Induced Cell Death Is Partly Caused by Increase of Mitochondrial Reactive Oxygen Species in Normal Human Fibroblast Cells

Radiation Research ◽

10.1667/rr13772.1 ◽

2015 ◽

Vol 183 (4) ◽

pp. 455 ◽

Cited By ~ 29

Author(s):

Shinko Kobashigawa ◽

Genro Kashino ◽

Keiji Suzuki ◽

Shunichi Yamashita ◽

Hiromu Mori

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Human Fibroblast ◽

Fibroblast Cells ◽

Oxygen Species ◽

Normal Human Fibroblast ◽

Mitochondrial Reactive Oxygen Species ◽

Human Fibroblast Cells ◽

Radiation Induced ◽

Normal Human

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Bystander Host Cell Killing Effects of Clostridium perfringens Enterotoxin

mBio ◽

10.1128/mbio.02015-16 ◽

2016 ◽

Vol 7 (6) ◽

Cited By ~ 4

Author(s):

Archana Shrestha ◽

Matthew R. Hendricks ◽

Jennifer M. Bomberger ◽

Bruce A. McClane

Keyword(s):

Cell Death ◽

Serine Protease ◽

Clostridium Perfringens ◽

Caspase 3 ◽

Host Cells ◽

Susceptible Host ◽

Cytotoxic Factor ◽

Killing Effect ◽

Bystander Killing

ABSTRACT Clostridium perfringens enterotoxin (CPE) binds to claudin receptors, e.g., claudin-4, and then forms a pore that triggers cell death. Pure cultures of host cells that do not express claudin receptors, e.g., fibroblasts, are unaffected by pathophysiologically relevant CPE concentrations in vitro . However, both CPE-insensitive and CPE-sensitive host cells are present in vivo . Therefore, this study tested whether CPE treatment might affect fibroblasts when cocultured with CPE-sensitive claudin-4 fibroblast transfectants or Caco-2 cells. Under these conditions, immunofluorescence microscopy detected increased death of fibroblasts. This cytotoxic effect involved release of a toxic factor from the dying CPE-sensitive cells, since it could be reproduced using culture supernatants from CPE-treated sensitive cells. Supernatants from CPE-treated sensitive cells, particularly Caco-2 cells, were found to contain high levels of membrane vesicles, often containing a CPE species. However, most cytotoxic activity remained in those supernatants even after membrane vesicle depletion, and CPE was not detected in fibroblasts treated with supernatants from CPE-treated sensitive cells. Instead, characterization studies suggest that a major cytotoxic factor present in supernatants from CPE-treated sensitive cells may be a 10- to 30-kDa host serine protease or require the action of that host serine protease. Induction of caspase-3-mediated apoptosis was found to be important for triggering release of the cytotoxic factor(s) from CPE-treated sensitive host cells. Furthermore, the cytotoxic factor(s) in these supernatants was shown to induce a caspase-3-mediated killing of fibroblasts. This bystander killing effect due to release of cytotoxic factors from CPE-treated sensitive cells could contribute to CPE-mediated disease. IMPORTANCE In susceptible host cells, Clostridium perfringens enterotoxin (CPE) binds to claudin receptors and then forms pores that result in cell death. Using cocultures of CPE receptor-expressing sensitive cells mixed with CPE-insensitive cells lacking receptors for this toxin, the current study determined that CPE-treated sensitive cells release soluble cytotoxic factors, one of which may be a 10- to 30-kDa serine protease, to cause apoptotic death of cells that are themselves CPE insensitive. These findings suggest a novel bystander killing mechanism by which a pore-forming toxin may extend its damage to affect cells not directly responsive to that toxin. If confirmed to occur in vivo by future studies, this bystander killing effect may have significance during CPE-mediated disease and could impact the translational use of CPE for purposes such as cancer therapy.

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Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages

Microbiology ◽

10.1099/mic.0.26341-0 ◽

2003 ◽

Vol 149 (9) ◽

pp. 2513-2527 ◽

Cited By ~ 34

Author(s):

Takashi Nonaka ◽

Taku Kuwabara ◽

Hitomi Mimuro ◽

Asaomi Kuwae ◽

Shinobu Imajoh-Ohmi

Keyword(s):

Cell Death ◽

Cell Membrane ◽

Host Cell ◽

Caspase 3 ◽

Cytochalasin D ◽

Host Cells ◽

U937 Cells ◽

Host Cell Membrane ◽

Caspase 1 ◽

Infected Cells

It is currently unclear whether Shigella kills its phagocytic host cells by apoptosis or necrosis. This study shows that rapid necrosis ensues in macrophage-like cell lines (U937 cells differentiated by all-trans-retinoic acid and J774 cells) infected with the Shigella flexneri strain YSH6000. The infected cells rapidly lose membrane integrity, a typical feature of necrosis, as indicated by the release of the cytoplasmic lactate dehydrogenase and the exposure of phosphatidylserine (PS) associated with the rapid uptake of propidium iodide (PI). The infected cells exhibit DNA fragmentation without nuclear condensation, and substantial involvement of either caspase-3/-7 or caspase-1 was not detected, which is also contrary to what is normally observed in apoptosis. Cytochalasin D potently inhibited Shigella-induced cell death, indicating that only internalized Shigella can cause necrosis. Osmoprotectants such as polyethylene glycols could suppress cell death, suggesting that insertion of a pore by Shigella into the host cell membrane induces the necrosis. The pore was estimated to be 2·87±0·4 nm in diameter. Shigella was also found to be able to induce apoptosis but only in one of the lines tested and under specific conditions, namely U937 cells differentiated with interferon-γ (U937IFN). Caspase-3/-7 but not caspase-1 activation was observed in these infected cells and the exposure of PS occurred without the uptake of PI. An avirulent Shigella strain, wild-type Shigella killed with gentamicin, and even Escherichia coli strain JM109, could also induce apoptosis in U937IFN cells, and cytochalasin D could not prevent apoptosis. It appears therefore that Shigella-induced apoptosis of U937IFN cells is unrelated to Shigella pathogenicity and does not require bacterial internalization. Thus, Shigella can induce rapid necrosis of macrophage-like cells in a virulence-related manner by forming pores in the host cell membrane while some cells can be killed through apoptosis in a virulence-independent fashion.

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