Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis
Mammalian cells do not produce chitin, an insoluble polymer of N-acetyl-D-glucosamine (GlcNAc), although chitin is a structural component of the cell wall of pathogenic microorganisms such as Candida albicans. Mammalian cells, including cells of the innate immune system elaborate chitinases, includi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.626798/full |
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| author | Nicholas A. Schmitz Ritesh P. Thakare Chun-Shiang Chung Chang-Min Lee Jack A. Elias Chun Geun Lee Brian W. LeBlanc |
| author_facet | Nicholas A. Schmitz Ritesh P. Thakare Chun-Shiang Chung Chang-Min Lee Jack A. Elias Chun Geun Lee Brian W. LeBlanc |
| author_sort | Nicholas A. Schmitz |
| collection | DOAJ |
| description | Mammalian cells do not produce chitin, an insoluble polymer of N-acetyl-D-glucosamine (GlcNAc), although chitin is a structural component of the cell wall of pathogenic microorganisms such as Candida albicans. Mammalian cells, including cells of the innate immune system elaborate chitinases, including chitotriosidase (Chit1), which may play a role in the anti-fungal immune response. In the current study, using knockout mice, we determined the role of Chit1 against systemic candidiasis. Chit1-deficient mice showed significant decrease in kidney fungal burden compared to mice expressing the functional enzyme. Using in vitro anti-candidal neutrophil functional assays, the introduction of the Chit1:chitin digestion end-product, chitobiose (N-acetyl-D-glucosamine dimer, GlcNAc2), decreased fungal-induced neutrophil swarming and Candida killing in vitro. Also, a role for the lectin-like binding site on the neutrophil integrin CR3 (Mac-1, CD11b/CD18) was found through physiological competitive interference by chitobiose. Furthermore, chitobiose treatment of wild type mice during systemic candidiasis resulted in the significant increase in fungal burden in the kidney. These data suggest a counterproductive role of Chit1 in mounting an efficient anti-fungal defense against systemic candidiasis. |
| first_indexed | 2024-12-16T20:10:03Z |
| format | Article |
| id | doaj.art-8e7c9cc3d9564937a46eab27077eb84e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T20:10:03Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8e7c9cc3d9564937a46eab27077eb84e2022-12-21T22:18:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.626798626798Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic CandidiasisNicholas A. Schmitz0Ritesh P. Thakare1Chun-Shiang Chung2Chang-Min Lee3Jack A. Elias4Chun Geun Lee5Brian W. LeBlanc6Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesMolecular Microbiology and Immunology, Brown University, Providence, RI, United StatesMolecular Microbiology and Immunology, Brown University, Providence, RI, United StatesMolecular Microbiology and Immunology, Brown University, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesMammalian cells do not produce chitin, an insoluble polymer of N-acetyl-D-glucosamine (GlcNAc), although chitin is a structural component of the cell wall of pathogenic microorganisms such as Candida albicans. Mammalian cells, including cells of the innate immune system elaborate chitinases, including chitotriosidase (Chit1), which may play a role in the anti-fungal immune response. In the current study, using knockout mice, we determined the role of Chit1 against systemic candidiasis. Chit1-deficient mice showed significant decrease in kidney fungal burden compared to mice expressing the functional enzyme. Using in vitro anti-candidal neutrophil functional assays, the introduction of the Chit1:chitin digestion end-product, chitobiose (N-acetyl-D-glucosamine dimer, GlcNAc2), decreased fungal-induced neutrophil swarming and Candida killing in vitro. Also, a role for the lectin-like binding site on the neutrophil integrin CR3 (Mac-1, CD11b/CD18) was found through physiological competitive interference by chitobiose. Furthermore, chitobiose treatment of wild type mice during systemic candidiasis resulted in the significant increase in fungal burden in the kidney. These data suggest a counterproductive role of Chit1 in mounting an efficient anti-fungal defense against systemic candidiasis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.626798/fullneutrophil (PMN)Candidacandidiasischitotriosidase (CHIT1)integrinsclustering |
| spellingShingle | Nicholas A. Schmitz Ritesh P. Thakare Chun-Shiang Chung Chang-Min Lee Jack A. Elias Chun Geun Lee Brian W. LeBlanc Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis Frontiers in Immunology neutrophil (PMN) Candida candidiasis chitotriosidase (CHIT1) integrins clustering |
| title | Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis |
| title_full | Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis |
| title_fullStr | Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis |
| title_full_unstemmed | Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis |
| title_short | Chitotriosidase Activity Is Counterproductive in a Mouse Model of Systemic Candidiasis |
| title_sort | chitotriosidase activity is counterproductive in a mouse model of systemic candidiasis |
| topic | neutrophil (PMN) Candida candidiasis chitotriosidase (CHIT1) integrins clustering |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.626798/full |
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