scholarly journals Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities

Parasite ◽  
2019 ◽  
Vol 26 ◽  
pp. 70 ◽  
Author(s):  
Sirous Mehrani Moghaddam ◽  
Stephane Picot ◽  
Ehsan Ahmadpour

Cystic echinococcosis and alveolar echinococcosis are chronic zoonotic infections, transmitted throughout the world. Development of the cestode larval stages in the liver and lungs causes damage to intermediate hosts, including humans. Several pathways leading to the suppression of host immune response and the survival of the cysts in various hosts are known. Immune response modulation and regulated cell death (RCD) play a fundamental role in cyst formation, development and pathogenesis. RCD, referring to apoptosis, necrosis and autophagy, can be triggered either via intrinsic or extrinsic cell stimuli. In this review, we provide a general overview of current knowledge on the process of RCD during echinococcosis. The study of interactions between RCD and Echinococcus spp. metacestodes may provide in-depth understanding of echinococcosis pathogenesis and open new horizons for human intervention and treatment of the disease.

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 982
Author(s):  
Samantha Sarcognato ◽  
Iris E. M. de Jong ◽  
Luca Fabris ◽  
Massimiliano Cadamuro ◽  
Maria Guido

Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.


2020 ◽  
Vol 8 (1) ◽  
pp. e000337 ◽  
Author(s):  
Lorenzo Galluzzi ◽  
Ilio Vitale ◽  
Sarah Warren ◽  
Sandy Adjemian ◽  
Patrizia Agostinis ◽  
...  

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.


2020 ◽  
Vol 21 (19) ◽  
pp. 7034
Author(s):  
Elena Butturini ◽  
Alessandra Carcereri de Prati ◽  
Sofia Mariotto

STAT1 and STAT3 are nuclear transcription factors that regulate genes involved in cell cycle, cell survival and immune response. The cross-talk between these signaling pathways determines how cells integrate the environmental signals received ultimately translating them in transcriptional regulation of specific sets of genes. Despite being activated downstream of common cytokine and growth factors, STAT1 and STAT3 play essentially antagonistic roles and the disruption of their balance directs cells from survival to apoptotic cell death or from inflammatory to anti-inflammatory responses. Different mechanisms are proposed to explain this yin-yang relationship. Considering the redox aspect of STATs proteins, this review attempts to summarize the current knowledge of redox regulation of STAT1 and STAT3 signaling focusing the attention on the post-translational modifications that affect their activity.


2020 ◽  
Vol 71 (2) ◽  
pp. 99-109
Author(s):  
Ivana Čepelak ◽  
Slavica Dodig ◽  
Daniela Čepelak Dodig

AbstractFerroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2612
Author(s):  
Lucie Cappuccio ◽  
Carine Maisse

Alphaviruses, such as the chikungunya virus, are emerging and re-emerging viruses that pose a global public health threat. They are transmitted by blood-feeding arthropods, mainly mosquitoes, to humans and animals. Although alphaviruses cause debilitating diseases in mammalian hosts, it appears that they have no pathological effect on the mosquito vector. Alphavirus/host interactions are increasingly studied at cellular and molecular levels. While it seems clear that apoptosis plays a key role in some human pathologies, the role of cell death in determining the outcome of infections in mosquitoes remains to be fully understood. Here, we review the current knowledge on alphavirus-induced regulated cell death in hosts and vectors and the possible role they play in determining tolerance or resistance of mosquitoes.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2637 ◽  
Author(s):  
Jean-David Fumet ◽  
Emeric Limagne ◽  
Marion Thibaudin ◽  
Francois Ghiringhelli

Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials.


2021 ◽  
Vol 15 (2) ◽  
pp. e0009120
Author(s):  
Muriel Rabone ◽  
Joris Wiethase ◽  
Paul F. Clark ◽  
David Rollinson ◽  
Neil Cumberlidge ◽  
...  

Paragonimiasis is caused by zoonotic trematodes of Paragonimus spp., found in Asia, the Americas and Africa, particularly in tropical regions. These parasites have a complex, multi-host life cycle, with mammalian definitive hosts and larval stages cycling through two intermediate hosts (snails and freshwater decapod crustaceans). In Africa, paragonimiasis is particularly neglected, and remains the only human parasitic disease without a fully characterised life cycle. However paragonimiasis has potentially significant impacts on public health in Africa, and prevalence has likely been underestimated through under-reporting and misdiagnosis as tuberculosis due to a similar clinical presentation. We identified the need to synthesise current knowledge and map endemic foci for African Paragonimus spp. together with Poikilorchis congolensis, a rare, taxonomically distant trematode with a similar distribution and morphology. We present the first systematic review of the literature relating to African paragonimiasis, combined with mapping of all reported occurrences of Paragonimus spp. throughout Africa, from the 1910s to the present. In human surveys, numerous reports of significant recent transmission in Southeast Nigeria were uncovered, with high prevalence and intensity of infection. Overall prevalence was significantly higher for P. uterobilateralis compared to P. africanus across studies. The potential endemicity of P. africanus in Côte d’Ivoire is also reported. In freshwater crab intermediate hosts, differences in prevalence and intensity of either P. uterobilateralis or P. africanus were evident across genera and species, suggesting differences in susceptibility. Mapping showed temporal stability of endemic foci, with the majority of known occurrences of Paragonimus found in the rainforest zone of West and Central Africa, but with several outliers elsewhere on the continent. This suggests substantial under sampling and localised infection where potential host distributions overlap. Our review highlights the urgent need for increased sampling in active disease foci in Africa, particularly using molecular analysis to fully characterise Paragonimus species and their hosts.


2019 ◽  
Vol 216 (7) ◽  
pp. 1474-1486 ◽  
Author(s):  
David E. Place ◽  
Thirumala-Devi Kanneganti

Targeting apoptosis to treat diseases has seen tremendous success over the past decades. More recently, alternative forms of regulated cell death, including pyroptosis and necroptosis, have been described. Understanding the molecular cascades regulating both pyroptosis and necroptosis will yield even more targets to treat diseases. These lytic forms of cell death are distinct from apoptosis due to their characteristic lysis and release of cellular components that promote disease or direct a beneficial immune response. In this review, we focus on how pyroptosis and necroptosis, which release potent immune cytokines such as IL-1 and IL-18, contribute to various diseases. We also consider the important role that the executioners of these cell death pathways, GSDMD and MLKL, play in the progression of inflammatory diseases. Crosstalk between the different cell death pathways likely plays a major role physiologically. New therapeutic strategies targeting these specific molecules hold enormous potential for managing inflammatory diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xinwen Wang ◽  
Shouwu Wu ◽  
Feng Liu ◽  
Dianshan Ke ◽  
Xinwu Wang ◽  
...  

Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients


2019 ◽  
Vol 1 (7) ◽  
pp. 29-32 ◽  
Author(s):  
L. S. Kruglova ◽  
E. M. Gensler

Over the past decades, the first breakthrough milestone in the treatment of severe forms of atopic dermatitis (AD) has been targeted therapy aimed at inhibiting IL-4 and IL-13. This was made possible thanks to advances in the understanding of the pathogenesis of AD, the driver of which is the Th2-type immune response, which also underlies such manifestations of atopy as bronchial asthma, allergic rhinitis, and polynosis. In the case of the Th2-type immune response, cytokines IL-4 and IL-13 are secreted, which are the main promoters of the inflammatory response in AD. Inhibition of IL-4 and IL-13 leads to the prevention of inflammation and is an effective approach to therapy. The use of therapy aimed at inhibition of cytokines allows you to effectively cope with the manifestations of severe and moderately severe blood pressure.


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