scholarly journals CD137 Signaling is Critical in Fungal Clearance During Systemic Candida albicans Infection

2021 ◽  
Author(s):  
Vu Vi Giang Tran ◽  
Zen Na Nu Nguyen ◽  
Byungsuk Kwon
Keyword(s):  
Innate Immunity ◽  
Candida Albicans ◽  
Defense Mechanisms ◽  
Tumor Necrosis ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Immunocompromised Patients ◽  
Agonistic Antibody ◽  
Innate Defense ◽  
Surface Receptor

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance at the early phase of infections, yet little has been known regarding which surface receptor controls neutrophil phagocytic activities during systemic C. albicans infection. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9-/- mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9-/- mice that received WT neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance whereby harmful immunopathology-induced tissue injuries are minimalized.

scholarly journals CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection

2021 ◽  
Vol 7 (5) ◽  
pp. 382
Author(s):  
Vuvi G. Tran ◽  
Na N. Z. Nguyen ◽  
Byungsuk Kwon
Keyword(s):  
Candida Albicans ◽  
Defense Mechanisms ◽  
Tumor Necrosis ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Wild Type ◽  
Agonistic Antibody ◽  
Innate Defense ◽  
Surface Receptor ◽  
Candida Albicans Infection

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9−/− mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9−/− mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.

scholarly journals Denture Stomatitis: Report of a Case with Rarely Used Treatment Modality and Review of Literature

2020 ◽  
Vol 4 (5) ◽  
pp. 116-119
Author(s):  
Parul Uppal Malhotra ◽  
Neera Ohri ◽  
Yagyeshwar Malhotra ◽  
Anindita Mallik
Keyword(s):  
Candida Albicans ◽  
Candida Species ◽  
Fungal Infections ◽  
Bacterial Colonization ◽  
Oral Candidiasis ◽  
Clinical Signs ◽  
Fungal Growth ◽  
Dimorphic Fungus ◽  
Denture Stomatitis ◽  
Microbial Invasion

Candida albicans is the most common Candida species isolated from the oral cavity both in healthy and diseased. Candida albicans is a dimorphic fungus existing both in blastopore phase (yeast phase) and the hyphal or mycelial phase. Although these organisms typically colonize mucocutaneous surfaces, the latter can be portals of entry into deeper tissues when host defences are compromised. Denture stomatitis is a common form of oral candidiasis that manifests as a diffuse inflammation of the maxillary denture bearing areas & is associated with angular cheilitis. At least 70% of individuals with clinical signs of denture stomatitis exhibit fungal growth & these conditions most likely result from yeast colonization of the oral mucosa combined with Bacterial colonization. Candida species act as an endogenous infecting agent on tissue predisposed by chronic trauma to microbial invasion. At one time, oral fungal infections were rare findings in general dentist's office. They were more commonly seen in hospitalized and severely debilitated patients. However with enhanced medical and pharmaceutical technology, increasing numbers of ambulatory immunosuppressed individuals with oral fungal infections are seeking out general dentists for diagnosis and treatment of these lesions.

scholarly journals The The Effects of Cinnamaldehyde (Cinnamon Derivatives) and Nystatin on Candida Albicans and Candida Glabrata

2019 ◽  
Vol 7 (7) ◽  
pp. 1067-1070 ◽  
Author(s):  
Sedigheh Bakhtiari ◽  
Soudeh Jafari ◽  
Jamileh Bigom Taheri ◽  
Tahereh Sadat Jafarzadeh Kashi ◽  
Zahra Namazi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Candida Species ◽  
Candida Glabrata ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Minimum Fungicidal Concentration ◽  
Microdilution Method

BACKGROUND: Candida species are the most common opportunistic fungal infections. Today, cinnamon plants have been considered for anti-Candida properties. AIM: This study aimed to investigate the effectiveness of cinnamaldehyde extract (from cinnamon derivatives) on Candida albicans and Candida glabrata species and comparison with nystatin. MATERIAL AND METHODS: In this study, cinnamaldehyde and nystatin were used. The specimens included Candida albicans and Candida glabrata. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured for each one by the microdilution method. This experiment was repeated three times. RESULTS: Cinnamaldehyde extract at a concentration of 62.5 μl/ml was able to prevent the growth of Candida albicans, at a concentration of 93.7 μl/ml, causing Candida albicans to disappear, at 48.8 μl/ml, to prevent the growth of Candida glabrata, and in the concentration of 62.5 μl/ml, causes the loss of Candida glabrata. In comparison, nystatin at 0.5 μg/ml concentration prevented the growth of Candida albicans, at concentrations of 1 μg/ml causing Candida albicans to be destroyed, at 4 μg/ml concentration to prevent the growth of Candida glabrata, and at a concentration of 8 μg/ml causes the loss of Candida glabrata. The results were the same every three times. CONCLUSIONS: Although cinnamaldehyde extract had an effect on fungal growth in both Candida albicans and Candida glabrata with a fatal effect; the effect on these two species was lower than nystatin.

scholarly journals Complement Attack againstAspergillusand Corresponding Evasion Mechanisms

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Cornelia Speth ◽  
Günter Rambach
Keyword(s):  
Innate Immunity ◽  
Complement Activation ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
First Line ◽  
Antifungal Effects ◽  
Risk Patients ◽  
The Complement System ◽  
Crucial Part

Invasive aspergillosis shows a high mortality rate particularly in immunocompromised patients. Perpetually increasing numbers of affected patients highlight the importance of a clearer understanding of interactions between innate immunity and fungi. Innate immunity is considered to be the most significant host defence against invasive fungal infections. Complement represents a crucial part of this first line defence and comprises direct effects against invading pathogens as well as bridging functions to other parts of the immune network. However, despite the potency of complement to attack foreign pathogens, the prevalence of invasive fungal infections is increasing. Two possible reasons may explain that phenomenon: First, complement activation might be insufficient for an effective antifungal defence in risk patients (due to, e.g., low complement levels, poor recognition of fungal surface, or missing interplay with other immune elements in immunocompromised patients). On the other hand, fungi may have developed evasion strategies to avoid recognition and/or eradication by complement. In this review, we summarize the most important interactions betweenAspergillusand the complement system. We describe the various ways of complement activation byAspergillusand the antifungal effects of the system, and also show proven and probable mechanisms ofAspergillusfor complement evasion.

scholarly journals In Vitro Interactions between Tacrolimus and Azoles against Candida albicans Determined by Different Methods

2007 ◽  
Vol 52 (2) ◽  
pp. 409-417 ◽  
Author(s):  
Shujuan Sun ◽  
Yan Li ◽  
Qiongjie Guo ◽  
Changwen Shi ◽  
Jinlong Yu ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Combination Therapy ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Detection Methods ◽  
Positive Interactions ◽  
Data Generation ◽  
Nonparametric Models ◽  
In Vitro Interactions

ABSTRACT Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi. However, the methods and approaches used for data generation and result interpretation need further optimizing. The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction. Alternatively, some new methods can be used such as the ΔE model (difference between the predicted and measured fungal growth percentages) and the response surface approach, which uses the concentration-effect relationship over the whole concentration range instead of just the MIC. In the present study, in vitro interactions between tacrolimus (FK506) and three azoles—fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida albicans were evaluated by the checkerboard microdilution method and time-killing test. The intensity of the interactions was determined by visual reading and the spectrophotometric method in a checkerboard assay, and the nature of the interactions was assessed by nonparametric models of FICI and ΔE. Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time. Synergistic and indifferent effects were found for the combination of FK506 and azoles against azole-sensitive strains, while strong synergy was found against azole-resistant strains analyzed by FICI. The ΔE model gave more consistent results with FICI. The positive interactions were also confirmed by the time-killing test. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant C. albicans.

scholarly journals Extending the Proteomic Characterization of Candida albicans Exposed to Stress and Apoptotic Inducers through Data-Independent Acquisition Mass Spectrometry

mSystems ◽  
2021 ◽  
Author(s):  
Ahinara Amador-García ◽  
Inés Zapico ◽  
Ana Borrajo ◽  
Johan Malmström ◽  
Lucía Monteoliva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Health Problem ◽  
Fungal Infections ◽  
Immunocompromised Patients ◽  
Content Type ◽  
Data Independent Acquisition ◽  
Chronic Disorders

Fungal infections are a worldwide health problem, especially in immunocompromised patients and patients with chronic disorders. Invasive candidiasis, caused mainly by C. albicans , is among the most common fungal diseases.

scholarly journals Dihydrofolate Reductase Is a Valid Target for Antifungal Development in the Human Pathogen Candida albicans

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Christian DeJarnette ◽  
Arturo Luna-Tapia ◽  
Leanna R. Estredge ◽  
Glen E. Palmer
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Dihydrofolate Reductase ◽  
Biosynthetic Pathway ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Content Type ◽  
Doxycycline Treatment ◽  
High Concentrations

ABSTRACT While the folate biosynthetic pathway has provided a rich source of antibacterial, antiprotozoal, and anticancer therapies, it has not yet been exploited to develop uniquely antifungal agents. Although there have been attempts to develop fungal-specific inhibitors of dihydrofolate reductase (DHFR), the protein itself has not been unequivocally validated as essential for fungal growth or virulence. The purpose of this study was to establish dihydrofolate reductase as a valid antifungal target. Using a strain with doxycycline-repressible transcription of DFR1 (PTETO-DFR1 strain), we were able to demonstrate that Dfr1p is essential for growth in vitro. Furthermore, nutritional supplements of most forms of folate are not sufficient to restore growth when Dfr1p expression is suppressed or when its activity is directly inhibited by methotrexate, indicating that Candida albicans has a limited capacity to acquire or utilize exogenous sources of folate. Finally, the PTETO-DFR1 strain was rendered avirulent in a mouse model of disseminated candidiasis upon doxycycline treatment. Collectively, these results confirm the validity of targeting dihydrofolate reductase and, by inference, other enzymes in the folate biosynthetic pathway as a strategy to devise new and efficacious therapies to combat life-threatening invasive fungal infections. IMPORTANCE The folate biosynthetic pathway is a promising and understudied source for novel antifungals. Even dihydrofolate reductase (DHFR), a well-characterized and historically important drug target, has not been conclusively validated as an antifungal target. Here, we demonstrate that repression of DHFR inhibits growth of Candida albicans, a major human fungal pathogen. Methotrexate, an antifolate, also inhibits growth but through pH-dependent activity. In addition, we show that C. albicans has a limited ability to take up or utilize exogenous folates as only the addition of high concentrations of folinic acid restored growth in the presence of methotrexate. Finally, we show that repression of DHFR in a mouse model of infection was sufficient to eliminate host mortality. Our work conclusively establishes DHFR as a valid antifungal target in C. albicans.

scholarly journals Interplay between Candida albicans and the Mammalian Innate Host Defense

2012 ◽  
Vol 80 (4) ◽  
pp. 1304-1313 ◽  
Author(s):  
Shih-Chin Cheng ◽  
Leo A. B. Joosten ◽  
Bart-Jan Kullberg ◽  
Mihai G. Netea
Keyword(s):  
Innate Immunity ◽  
Candida Albicans ◽  
Host Defense ◽  
High Mortality ◽  
Fungal Pathogen ◽  
Immunocompromised Patients ◽  
Healthy Individuals ◽  
Content Type ◽  
At Risk Populations ◽  
Host Innate Immunity

ABSTRACTCandida albicansis both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system andC. albicans, ranging from how the host recognizes, responds, and clearsC. albicansinfection to howC. albicansevades, dampens, and escapes from host innate immunity.

scholarly journals Immune cells fold and damage fungal hyphae

2021 ◽  
Vol 118 (15) ◽  
pp. e2020484118
Author(s):  
Judith M. Bain ◽  
M. Fernanda Alonso ◽  
Delma S. Childers ◽  
Catriona A. Walls ◽  
Kevin Mackenzie ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Candida Albicans ◽  
Immune Cells ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Hyphal Growth ◽  
Β2 Integrin ◽  
Cellular Morphogenesis ◽  
Fungal Hyphae ◽  
Life Threatening

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans–macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin–myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.

Ultrastructural Changes of Candida albicans Species Induced by the Presence of Sodium Diclofenac

2017 ◽  
Vol 68 (11) ◽  
pp. 2566-2569 ◽  
Author(s):  
Elena Rusu ◽  
Ionela Sarbu ◽  
Magdalena Mitache ◽  
Horatiu Moldovan ◽  
Carmen Ioana Biris ◽  
...  
Keyword(s):  
Candida Albicans ◽  
High Frequency ◽  
Fungal Infections ◽  
Diagnostic Methods ◽  
Ultrastructural Changes ◽  
Frequency Of Occurrence ◽  
Medical Treatments ◽  
Sodium Diclofenac ◽  
Cell Wall Disruption ◽  
Candidiasis Treatment

The high frequency of occurrence of candidiasis as well as high mortality of patients with immunosuppression cause a tendency toward better understanding of Candida albicans species virulence factors and developing sensitive and specific diagnostic methods, and appropriate strategies of candidiasis treatment. In recent decades the incidence of fungal infections has alarming increases because of advanced medical treatments. In this study was analyzed possible ultrastructural changes of the species C. albicans cells following treatment with sodium diclofenac at various concentrations. Following treatment of C. albicans cells with sodium diclofenac 1 mM and 2 mM changes in the plasmalemma can be noticed, changes in the density of cell wall, disruption and necrotic appearance of the cytoplasm.

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