Activation-dependent cell death of human monocytes is a novel mechanism of fine-tuning inflammation and autoimmunity

Abstract Salicylic acid (SA) is required for resistance to many diseases in higher plants. SA-dependent cell death and defense-related responses have been correlated with disease resistance. The accelerated cell death 5 mutant of Arabidopsis provides additional genetic evidence that SA regulates cell death and defense-related responses. However, in acd5, these events are uncoupled from disease resistance. acd5 plants are more susceptible to Pseudomonas syringae early in development and show spontaneous SA accumulation, cell death, and defense-related markers later in development. In acd5 plants, cell death and defense-related responses are SA dependent but they do not confer disease resistance. Double mutants with acd5 and nonexpressor of PR1, in which SA signaling is partially blocked, show greatly attenuated cell death, indicating a role for NPR1 in controlling cell death. The hormone ethylene potentiates the effects of SA and is important for disease symptom development in Arabidopsis. Double mutants of acd5 and ethylene insensitive 2, in which ethylene signaling is blocked, show decreased cell death, supporting a role for ethylene in cell death control. We propose that acd5 plants mimic P. syringae-infected wild-type plants and that both SA and ethylene are normally involved in regulating cell death during some susceptible pathogen infections.

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Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death

Nature Cell Biology ◽

10.1038/ncb1575 ◽

2007 ◽

Vol 9 (5) ◽

pp. 550-555 ◽

Cited By ~ 645

Author(s):

Christopher P. Baines ◽

Robert A. Kaiser ◽

Tatiana Sheiko ◽

William J. Craigen ◽

Jeffery D. Molkentin

Keyword(s):

Cell Death ◽

Anion Channels ◽

Voltage Dependent ◽

Dependent Cell

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Human Herpesvirus 6A Induces Dendritic Cell Death and HMGB1 Release without Virus Replication

Pathogens ◽

10.3390/pathogens10010057 ◽

2021 ◽

Vol 10 (1) ◽

pp. 57

Author(s):

Rasmus Gustafsson

Keyword(s):

Cell Death ◽

Dendritic Cells ◽

High Mobility ◽

Human Herpesvirus ◽

Human Monocyte ◽

Hmgb1 Protein ◽

Innate And Adaptive Immunity ◽

Th2 Polarization ◽

Dependent Cell ◽

Ifn Γ

Human herpesvirus 6A (HHV-6A) is a common virus that has important immunomodulatory effects. Dendritic cells (DC) are key players in innate and adaptive immunity and are implicated in the pathogenesis of many human diseases, including infections. (1) Background: Previous studies have demonstrated suppressive effects of HHV-6A on key DC functions. (2) Methods: human monocyte derived dendritic cells were inoculated with HHV-6A and viral replication, cell viability, and release of high mobility group box 1 (HMGB1) protein from DC and of the cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ after co-culture with allogenic CD4+ T cells were assessed. (3) Results: Nonproductive infection of HHV-6A in DC leads to titer-dependent cell death and the release of HMGB1 protein, and a Th2 polarization. (4) Conclusion: These immune responses aimed to clear the infection may also imply risks for inflammatory pathologies associated with HHV-6A such as multiple sclerosis.

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