Necroptotic signaling in adaptive and innate immunity

Lu, Jennifer; Chen, Helen C.; Walsh, Craig M.

doi:10.1016/j.semcdb.2014.07.003

Cited by 61 publications

(55 citation statements)

References 103 publications

(133 reference statements)

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“…In contrast, apoptosis relies on a ripoptosome complex with FADD, RIPK-3, RIPK-1, and active caspase 8. 21 The cytosol of unstimulated PMN contained ripoptosomes composed of FADD, RIPK-3, RIPK-1, and caspase 8 (PMN 0 h in Figure 1C). Furthermore, the association of FADD, RIPK-3, and RIPK-1 with full-length caspase 8 did not vary over time in either control PMN or PMN-SA ( Figure 1C), and the caspase 8 recovered is inactive during lysis of PMN-SA, as we reported previously.…”

Section: Tnfa and Lysis Of Pmn-samentioning

confidence: 99%

Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus

Greenlee‐Wacker

Kremserová

Nauseef

2017

Blood

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Community-associated methicillin-resistant (CA-MRSA) causes infections associated with extensive tissue damage and necrosis. In vitro, human neutrophils fed CA-MRSA lyse by an unknown mechanism that is inhibited by necrostatin-1, an allosteric inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK-1). RIPK-1 figures prominently in necroptosis, a specific form of programmed cell death dependent on RIPK-1, RIPK-3, and the mixed-lineage kinase-like protein (MLKL). We previously reported that necrostatin-1 inhibits lysis of human neutrophils fed CA-MRSA and attributed the process to necroptosis. We now extend our studies to examine additional components in the programmed cell death pathway to test the hypothesis that neutrophils fed CA-MRSA undergo necroptosis. Lysis of neutrophils fed CA-MRSA was independent of tumor necrosis factor α, active RIPK-1, and MLKL, but dependent on active RIPK-3. Human neutrophils fed CA-MRSA lacked phosphorylated RIPK-1, as well as phosphorylated or oligomerized MLKL. Neutrophils fed CA-MRSA possessed cytoplasmic complexes that included inactive caspase 8, RIPK-1, and RIPK-3, and the composition of the complex remained stable over time. Together, these data suggest that neutrophils fed CA-MRSA underwent a novel form of lytic programmed cell death via a mechanism that required RIPK-3 activity, but not active RIPK-1 or MLKL, and therefore was distinct from necroptosis. Targeting the molecular pathways that culminate in lysis of neutrophils during CA-MRSA infection may serve as a novel therapeutic intervention to limit the associated tissue damage.

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Section: Tnfa and Lysis Of Pmn-samentioning

confidence: 99%

Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus

Greenlee‐Wacker

Kremserová

Nauseef

2017

Blood

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“…Although the main pathway of cell death stimulated by DRs is apoptosis, DRs can also cause an increased permeability of the cell plasma membrane and form necrosomes and necrotic-like cell death (Mocarski, Kaiser, Livingston-Rosanoff, Upton, & Daley-Bauer, 2014). Necroptosis occurs where caspase8 is not expressed or it's activation on the DISC is disturbed (Lu, Chen, & Walsh, 2014). The DR signaling pathway is one of the major tumor immune-editing mechanisms.…”

Section: Death Receptor Signaling Pathwaymentioning

confidence: 99%

Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

Marjaneh

Hassanian

Ghobadi

et al. 2018

Journal Cellular Physiology

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Despite advances in the diagnosis and treatment of colorectal cancer (CRC), it remains a major cause of cancer related death globally. There are currently no chemotherapeutic agents that have been found to eradicate the disease without adverse effects. A defect in the death receptor signaling pathway is a feature of CRC. The ligand of these receptors belongs to the tumor necrosis factor family, and that are particularly expressed by cells of the immune system, and that induce apoptosis in a caspase dependent manner. The fact that malignant cells are particularly sensitive to these ligands, compared to normal cells, has led to work on the assessment of compounds that activate this pathway in the treatment of CRC. Phase I trials have shown that these death receptor agonists are safe. Phase II and III trials are currently investigating the efficacy of these therapeutic agents in the treatment of CRC. In this review, we describe the biochemical death receptor signaling pathway and its relationship to CRC. We also summarize the current clinical studies that are targeting this signaling pathway in CRC treatment.

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“…It should be noted that the preferential form of cell death induced by DRs is apoptosis, and the formation of the necrosome is only permitted in scenarios where caspase-8 is either not expressed (49) or its activation in the DISC fails (54). When active, caspase-8 cleaves RIPK1 within its kinase domains (KDs) and intermediate domains (IDs), thus blocking its function (55) (Figure 2).…”

Section: The Role Of Death Ligands In Tumor Immune Eliminationmentioning

confidence: 99%

The Janus Face of Death Receptor Signaling during Tumor Immunoediting

et al. 2016

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Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family. However, some tumor cells can escape immune elimination and progress. Acquisition of resistance to the death ligand-induced apoptotic pathway can be obtained through cleavage of effector cell expressed death ligands into a poorly active form, mutations or silencing of the death receptors, or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/dysfunctional death ligand signaling curbs its cytotoxicity. Moreover, DRs can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signaling does not only give a passive resistance against cell death but actively drives tumor cell motility, invasion, and contributes to consequent metastasis. This dual contribution of the death receptor signaling in both the early, elimination phase, and then in the late, escape phase of the tumor immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumor-eliminating immune effector function even in the absence of activation of the immune system against the tumor. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.

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Necroptotic signaling in adaptive and innate immunity

Cited by 61 publications

References 103 publications

Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus

Lysis of human neutrophils by community-associated methicillin-resistant Staphylococcus aureus

Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

The Janus Face of Death Receptor Signaling during Tumor Immunoediting

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