Programmed Cell Death: Central Player in Fungal Infections

Camilli, Giorgio; Blagojevic, Mariana; Naglik, Julian R.; Richardson, Jonathan P.

doi:10.1016/j.tcb.2020.11.005

Cited by 23 publications

(23 citation statements)

References 102 publications

(167 reference statements)

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“… 21 , 22 Till now, a total of 5 types of inflammasomes have been identified, namely NLRP1 inflammasome, NLRP3 inflammasome, NLRC4 inflammasome, IPAF inflammasome and absent in melanoma 2 (AIM2) inflammasome. 23 Generally, one inflammasome generally contains an apoptosis-associated speck-like protein containing CARD, ASC, caspase protease, and NLR family protein (such as NLRP1) or HIN200 family protein (such as AIM2). 4 , 24 , 25 Kovarova et al 26 disclosed that assembly of the NLRP1 inflammasome could initiate pyroptosis, which then gives rise to a self-amplifying cascade of lung injury triggered by a toxin from anthrax, eventually causing catastrophic consequences.…”

Section: Discussionmentioning

confidence: 99%

Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Li¹,

Xiong²,

He³

et al. 2021

JIR

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Scope Mangiferin (MF) is a natural phytopolyphenol, which displays potential pharmacological properties involving antibacterial, anti-inflammation, antioxidant and anti-tumor. However, little is known about the roles of MF in lung injury. The aim of this study is to demonstrate the modulatory effects and molecular mechanisms by which MF operates in sepsis-induced lung injury. Methods and Results To examine the protective properties of MF, an in vivo model of lipopolysaccharide (LPS)-induced lung injury in mice and an in vitro model of LPS-treated J774A.1 cells were established, respectively. The results revealed that MF treatment significantly relieved LPS-induced pathological injury and inflammatory response in murine lung tissues. Meanwhile, MF treatment also inhibited nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation and pyroptosis induced by LPS. In macrophage-specific NLRP3 deficiency mice treated with LPS, MF showed little protective effects. NLRP3 overexpression by adenovirus could also offset the beneficial effects of MF in LPS-treated J774A.1 cells. Furthermore, we found that MF could suppress the expression of NLPR3 and pyroptosis of macrophages by inhibiting the nuclear translocation of the nuclear factor-κB (NF-κB) subunits P50 and P65. Conclusion MF protects against lung injury and inflammatory response by inhibiting NLRP3 inflammasome activation in a NF-κB-dependent manner in macrophages, which provides a promising therapeutic candidate for the treatment of lung injury.

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Section: Discussionmentioning

confidence: 99%

Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Li¹,

Xiong²,

He³

et al. 2021

JIR

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“…Live C. albicans induced early apoptotic signalling events in oral epithelial cells and macrophages followed by necrotic death (Panagio, Felipe, Vidotto, & Gaziri, 2002; Villar & Zhao, 2010). Furthermore, necrotic pathways that promote lytic cell death have been recently described in myeloid cells following Candida infection (Camilli et al, 2020; Cao et al, 2019; Kasper et al, 2018; O'Meara et al, 2015; O'Meara et al, 2018; Tucey et al, 2020; Uwamahoro et al, 2014; Vylkova & Lorenz, 2017; Wellington, Koselny, Sutterwala, & Krysan, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…C. albicans possesses a multitude of virulence factors (Richardson, Ho, & Naglik, 2018) but the secretion of the peptide toxin candidalysin (encoded by the ECE1 gene) is a key driver of cell damage and immune responses in mucosal and systemic models of C. albicans infection (Aggor et al, 2020; Allert et al, 2018; Drummond et al, 2019; Ho et al, 2019; Ho et al, 2020; Kasper et al, 2018; Moyes et al, 2016; Richardson et al, 2018; Richardson et al, 2018; Swidergall et al, 2019; Verma et al, 2017; Verma et al, 2018). Cell damage often results in cell stress and ultimately death, which can play a key role in host defence to microbial infections (Camilli, Blagojevic, Naglik, & Richardson, 2020; Jorgensen, Rayamajhi, & Miao, 2017). Furthermore, pathogens have evolved several strategies to induce or inhibit host cell death, aiding dissemination and survival within the host.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, pathogens have evolved several strategies to induce or inhibit host cell death, aiding dissemination and survival within the host. Cell death can be driven by several biological processes including apoptosis, autophagy and different types of necrotic cell death, which can influence the outcome of a microbial insult (Camilli et al, 2020; Jorgensen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…While induction of apoptosis and necrotic cell death has predominantly been investigated in the context of viral and bacterial infections (Jorgensen et al, 2017), their importance during fungal diseases has only recently been recognised. In addition, data regarding induction or manipulation of cell death pathways during the interplay between pathogenic fungi and host cells are more limited (Camilli et al, 2020). Thus far, few components have been proposed to play a role in the induction of apoptosis in immune and non‐immune cells in response to C. albicans .…”

Section: Introductionmentioning

confidence: 99%

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Candidalysin triggers epithelial cellular stresses that induce necrotic death

Blagojevic

Camilli

Maxson

et al. 2021

Cellular Microbiology

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Candida albicans is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin‐induced cell death remains unclear. Here, we examined the induction of cell death by candidalysin in oral epithelial cells. Fluorescent imaging using healthy/apoptotic/necrotic cell markers revealed that candidalysin causes a rapid and marked increase in the population of necrotic rather than apoptotic cells in a concentration dependent manner. Activation of a necrosis‐like pathway was confirmed since C. albicans and candidalysin failed to activate caspase‐8 and ‐3, or the cleavage of poly (ADP‐ribose) polymerase. Furthermore, oral epithelial cells treated with candidalysin showed rapid production of reactive oxygen species, disruption of mitochondria activity and mitochondrial membrane potential, ATP depletion and cytochrome c release. Collectively, these data demonstrate that oral epithelial cells respond to the secreted fungal toxin candidalysin by triggering numerous cellular stress responses that induce necrotic death. Take aways Candidalysin secreted from Candida albicans causes epithelial cell stress. Candidalysin induces calcium influx and oxidative stress in host cells. Candidalysin induces mitochondrial dysfunction, ATP depletion and epithelial necrosis. The toxicity of candidalysin is mediated from the epithelial cell surface.

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Virulence of Pathogens and the Counteracting Responses of the Host

Land

2023

Damage-Associated Molecular Patterns in Human Diseases

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Programmed Cell Death: Central Player in Fungal Infections

Cited by 23 publications

References 102 publications

Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Mangiferin Mitigates Lipopolysaccharide-Induced Lung Injury by Inhibiting NLRP3 Inflammasome Activation

Candidalysin triggers epithelial cellular stresses that induce necrotic death

Virulence of Pathogens and the Counteracting Responses of the Host

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