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

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.

Author(s):  
Vu Vi Giang Tran ◽  
Zen Na Nu Nguyen ◽  
Byungsuk Kwon

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.


2020 ◽  
Vol 4 (5) ◽  
pp. 116-119
Author(s):  
Parul Uppal Malhotra ◽  
Neera Ohri ◽  
Yagyeshwar Malhotra ◽  
Anindita Mallik

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.


2019 ◽  
Vol 7 (7) ◽  
pp. 1067-1070 ◽  
Author(s):  
Sedigheh Bakhtiari ◽  
Soudeh Jafari ◽  
Jamileh Bigom Taheri ◽  
Tahereh Sadat Jafarzadeh Kashi ◽  
Zahra Namazi ◽  
...  

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.


1997 ◽  
Vol 22 (3) ◽  
pp. 423-424 ◽  
Author(s):  
A. B. DUNKLEY ◽  
I. J. LESLIE

Fungal infections following joint arthroplasty are extremely rare. Only 16 cases of Candida prosthetic infections have been reported, involving the hip, knee or shoulder joints. We report a case of a silicone metacarpophalangeal joint replacement complicated by a Candida albicans infection.


2000 ◽  
Vol 76 (4) ◽  
pp. 257-262 ◽  
Author(s):  
José B Da Silva ◽  
Cleide M.R De Albuquerque ◽  
Eva Cristina De Araújo ◽  
Christina A Peixoto ◽  
Hilary Hurd

2022 ◽  
pp. ji2100495
Author(s):  
Nu Z. N. Nguyen ◽  
Vuvi G. Tran ◽  
Jiyeon Baek ◽  
Younghee Kim ◽  
Eun H. Youn ◽  
...  

2002 ◽  
Vol 70 (5) ◽  
pp. 2614-2621 ◽  
Author(s):  
Angela van Diepen ◽  
Tahar van der Straaten ◽  
Steven M. Holland ◽  
Riny Janssen ◽  
Jaap T. van Dissel

ABSTRACT Salmonella enterica serovar Typhimurium is a gram-negative, facultative intracellular pathogen that predominantly invades mononuclear phagocytes and is able to establish persistent infections. One of the innate defense mechanisms of phagocytic cells is the production of reactive oxygen species, including superoxide. S. enterica serovar Typhimurium has evolved mechanisms to resist such radicals, and these mechanisms could be decisive in its ability to survive and replicate within macrophages. Recently, we described a superoxide-hypersusceptible S. enterica serovar Typhimurium mutant strain, DLG294, that carries a transposon in sspJ, resulting in the lack of expression of SspJ, which is necessary for resistance against superoxide and replication within macrophages. Here we show that DLG294, which is a 14028s derivative, hardly induced any granulomatous lesions in the livers upon subcutaneous infection of C3H/HeN (Ityr) mice with 3 × 104 bacteria and that its bacterial counts were reduced by 3 log units compared to those of wild-type S. enterica serovar Typhimurium 14028s on day 5 after infection. In contrast, DLG294 replicated like wild-type S. enterica serovar Typhimurium 14028s and induced a phenotypically similar liver pathology in p47phox−/− mice, which are deficient in the p47phox subunit of the NADPH oxidase complex and which do not produce superoxide. Consistent with these results, DLG294 reached bacterial counts identical to those of wild-type S. enterica serovar Typhimurium 14028s in bone marrow-derived macrophages from p47phox−/− mice and in X-CGD PLB-985 cells at 24 h after challenge. These results indicate that SspJ plays a role in the bacterium's resistance to oxidative stress and in the survival and replication of S. enterica serovar Typhimurium both in vitro and in vivo.


2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Sahar Hasim ◽  
David P. Allison ◽  
Scott T. Retterer ◽  
Alex Hopke ◽  
Robert T. Wheeler ◽  
...  

ABSTRACT Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.


1993 ◽  
Vol 167 (5) ◽  
pp. 1168-1172 ◽  
Author(s):  
R. Allendoerfer ◽  
D. M. Magee ◽  
J. G. Smith ◽  
L. Bonewald ◽  
J. R. Graybill

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