Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

Davidson, Linda; Netea, Mihai G.; Kullberg, Bart Jan

doi:10.3390/jof4010009

Cited by 26 publications

(22 citation statements)

References 139 publications

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“…In addition to the inhibition by gut microbiota, neutrophil can also provide protection against Candida invasion by killing engulfed fungi through oxidative and non-oxidative mechanisms, or by trapping extracellular fungi by neutrophil extracellular traps (NETs) ( Netea et al, 2015 ; Davidson et al, 2018 ). If the hyphal form grows excessively, epithelial cells can produce inflammatory mediators to recruit innate immune cells to clear fungal infections ( Naglik et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model

Pan

Yan

et al. 2021

Front. Microbiol.

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Candida albicans is the leading cause of candidemia or other invasive candidiasis. Gastrointestinal colonization has been considered as the primary source of candidemia. However, few established mouse models that mimic this infection route are available. In the present study, we established a mouse model of disseminated candidiasis developed through the translocation of Candida from the gut. In this study, we developed a novel C. albicans GI colonization and dissemination animal model by using severe combined immunodeficient Rag2–/–IL2γc–/– (Rag2γc) mice, which lack functional T, B, NK cells, and IL2γc-dependent signaling. Rag2γc mice were highly susceptible to C. albicans gastrointestinal infection even in the presence of the gut microbiota. Within 4 weeks post infection, Rag2γc mice showed dose-dependent weight loss and disseminated candidiasis in more than 58% (7/12) of moribund mice. Histological analysis demonstrated abundant hyphae penetrating the mucosa, with significant neutrophilic infiltration in mice infected with wild-type C. albicans but not a filamentation-defective mutant. In moribund Rag2γc mice, the necrotic lesions and disrupted epithelial cells were associated with C. albicans hyphae. Notably, removal of the gut microbiota by antibiotics exacerbated the severity of fungal infection in Rag2γc mice, as demonstrated by elevated fungal burdens and accelerated weight loss and death. Furthermore, higher fungal burden and IL-1β expression were prominently noted in the stomach of Rag2γc mice. In fact, a significant increase in circulating proinflammatory cytokines, including IL-6, TNF-α, and IL-10, indicative of a septic response, was evident in infected Rag2γc mice. Additionally, Rag2γc mice exhibited significantly lower levels of IL-22 but not IFN-γ or IL-17A than wild-type B6 mice, suggesting that IL-22 plays a role in C. albicans gastrointestinal infection. Collectively, our analysis of the Rag2γc mouse model revealed features of C. albicans gastrointestinal colonization and dissemination without the interference from antibiotics or chemotherapeutic agents, thus offering a new investigative tool for delineating the pathogenesis of C. albicans and its cross-talk with the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model

Pan

Yan

et al. 2021

Front. Microbiol.

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“…These pathogens and their byproducts can trigger inflammasome activation. Candida spp., frequently found in peri-implantitis lesions, can induce activation of the NLRP3 inflammasome (282). LPS from P. gingivalis, another peri-implantitis-related pathogen, increases the mRNA levels of NLRP3, ASC, and caspase-1 in BMSCs, thereby increasing IL-1b production (147).…”

Section: Inflammasomes In Peri-implantitismentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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“…Nevertheless, clinical evidence has shown that dental prosthetic devices, mainly based on PMMA resins, undergo a proliferation of C. albicans infections [3,4,5], which affects their lifetime. Indeed, C. albicans is a pleomorphic fungus that is commensal of gastrointestinal microbiota [5] and, in case of immunodeficiency, the frequency of candidiasis can increase [6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Silver Nanoparticles Addition in Poly(Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies

Matteis

Cascione

Toma

et al. 2019

IJMS

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The widespread use of nanoparticles (NPs) in medical devices has opened a new scenario in the treatment and prevention of many diseases and infections owing to unique physico-chemical properties of NPs. In this way, silver nanoparticles (AgNPs) are known to have a strong antimicrobial activity, even at low concentrations, due to their ability to selectively destroy cellular membranes. In particular, in the field of dental medicine, the use of AgNPs in different kinds of dental prosthesis matrixes could be a fundamental tool in immunodepressed patients that suffer of different oral infections. Candida albicans (C. albicans), an opportunistic pathogenic yeast with high colonization ability, is one of the causative agents of oral cavity infection. In our work, we added monodispersed citrate-capping AgNPs with a size of 20 nm at two concentrations (3 wt% and 3.5 wt%) in poly(methyl methacrylate) (PMMA), the common resin used to develop dental prostheses. After AgNPs characterization, we evaluated the topographical modification of PMMA and PMMA with the addition of AgNPs by means of atomic force microscopy (AFM), showing the reduction of surface roughness. The C. albicans colonization on PMMA surfaces was assessed by the Miles and Misra technique as well as by scanning electron microscopy (SEM) at 24 h and 48 h with encouraging results on the reduction of yeast viability after AgNPs exposure.

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Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy

Cited by 26 publications

References 139 publications

Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model

Candida albicans Colonizes and Disseminates to the Gastrointestinal Tract in the Presence of the Microbiota in a Severe Combined Immunodeficient Mouse Model

Inflammasomes in Alveolar Bone Loss

Silver Nanoparticles Addition in Poly(Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies

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