CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection

Invasive fungal infections by <i>Candida albicans</i> frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic <i>C. albican</i> infection, yet little has been known regarding which surface receptor...

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Main Authors: Vuvi G. Tran, Na N. Z. Nguyen, Byungsuk Kwon
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/7/5/382
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author Vuvi G. Tran
Na N. Z. Nguyen
Byungsuk Kwon
author_facet Vuvi G. Tran
Na N. Z. Nguyen
Byungsuk Kwon
author_sort Vuvi G. Tran
collection DOAJ
description Invasive fungal infections by <i>Candida albicans</i> frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic <i>C. albican</i> infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by <i>Tnfrsf9</i>, 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 <i>C. albicans</i> infection. We first found that <i>Tnfrsf9</i><sup>−/−</sup> mice were susceptible to <i>C. albicans</i> infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against <i>C. albicans</i> 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 <i>Tnfrsf9</i><sup>−/−</sup> mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic <i>C. albicans</i> infection by promoting rapid fungal clearance.
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spelling doaj.art-835f06cf8f8e4681afe08a337a5df3672023-11-21T19:42:59ZengMDPI AGJournal of Fungi2309-608X2021-05-017538210.3390/jof7050382CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> InfectionVuvi G. Tran0Na N. Z. Nguyen1Byungsuk Kwon2School of Biological Science, University of Ulsan, Ulsan 44610, KoreaSchool of Biological Science, University of Ulsan, Ulsan 44610, KoreaSchool of Biological Science, University of Ulsan, Ulsan 44610, KoreaInvasive fungal infections by <i>Candida albicans</i> frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic <i>C. albican</i> infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by <i>Tnfrsf9</i>, 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 <i>C. albicans</i> infection. We first found that <i>Tnfrsf9</i><sup>−/−</sup> mice were susceptible to <i>C. albicans</i> infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against <i>C. albicans</i> 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 <i>Tnfrsf9</i><sup>−/−</sup> mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic <i>C. albicans</i> infection by promoting rapid fungal clearance.https://www.mdpi.com/2309-608X/7/5/382<i>Candida albicans</i>CD137neutrophilfungal clearance
spellingShingle Vuvi G. Tran
Na N. Z. Nguyen
Byungsuk Kwon
CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
Journal of Fungi
<i>Candida albicans</i>
CD137
neutrophil
fungal clearance
title CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
title_full CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
title_fullStr CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
title_full_unstemmed CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
title_short CD137 Signaling Is Critical in Fungal Clearance during Systemic <i>Candida albicans</i> Infection
title_sort cd137 signaling is critical in fungal clearance during systemic i candida albicans i infection
topic <i>Candida albicans</i>
CD137
neutrophil
fungal clearance
url https://www.mdpi.com/2309-608X/7/5/382
work_keys_str_mv AT vuvigtran cd137signalingiscriticalinfungalclearanceduringsystemicicandidaalbicansiinfection
AT nanznguyen cd137signalingiscriticalinfungalclearanceduringsystemicicandidaalbicansiinfection
AT byungsukkwon cd137signalingiscriticalinfungalclearanceduringsystemicicandidaalbicansiinfection