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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MDPI AG
2021-05-01
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Series: | Journal of Fungi |
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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. |
first_indexed | 2024-03-10T11:24:56Z |
format | Article |
id | doaj.art-835f06cf8f8e4681afe08a337a5df367 |
institution | Directory Open Access Journal |
issn | 2309-608X |
language | English |
last_indexed | 2024-03-10T11:24:56Z |
publishDate | 2021-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Journal of Fungi |
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 |
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