In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice

Beta-glucan (β-glucan) is a natural polysaccharide produced by fungi, bacteria, and plants. Although it has been reported that β-glucan enhances innate immune memory responses, it is unclear whether different types of β-glucans display similar immune effects. To address this issue, we employed zymos...

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Main Authors: Hyun Jung Park, Sung Won Lee, Yun Hoo Park, Tae-Cheol Kim, Sujin Lee, Seyeong Lee, Luc Van Kaer, Seokmann Hong
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/15/5779
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author Hyun Jung Park
Sung Won Lee
Yun Hoo Park
Tae-Cheol Kim
Sujin Lee
Seyeong Lee
Luc Van Kaer
Seokmann Hong
author_facet Hyun Jung Park
Sung Won Lee
Yun Hoo Park
Tae-Cheol Kim
Sujin Lee
Seyeong Lee
Luc Van Kaer
Seokmann Hong
author_sort Hyun Jung Park
collection DOAJ
description Beta-glucan (β-glucan) is a natural polysaccharide produced by fungi, bacteria, and plants. Although it has been reported that β-glucan enhances innate immune memory responses, it is unclear whether different types of β-glucans display similar immune effects. To address this issue, we employed zymosan (β-1,3-glycosidic linkage) and pustulan (β-1,6-glycosidic linkage) to investigate their in vivo effects on innate memory immune responses. We examined the changes of innate memory-related markers in macrophages and natural killer (NK) cells, two immune cell types that display innate memory characteristics, at two different time points (16 h and 7 days) after β-glucan stimulation. We found that short-term (16 h) zymosan treatment significantly induced macrophages to upregulate IL15 production and increased surface IL15Rα expression on NK cells. In addition, long-term (7 days) zymosan treatment significantly induced macrophages to upregulate the expression of innate memory-related markers (e.g., TNFα, HIF1α, and mTOR) and induced NK cells to express enhanced levels of KLRG1, known as an innate memory-like marker. Our results provide support that zymosan can be an effective adjuvant to promote innate memory immune responses, providing a bridge between innate and adaptive immune cells to enhance various immune responses such as those directed against tumors.
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spelling doaj.art-141e6de8fa024154a491202c58ca89302023-11-18T23:18:46ZengMDPI AGMolecules1420-30492023-07-012815577910.3390/molecules28155779In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in MiceHyun Jung Park0Sung Won Lee1Yun Hoo Park2Tae-Cheol Kim3Sujin Lee4Seyeong Lee5Luc Van Kaer6Seokmann Hong7Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Biomedical Laboratory Science, College of Health and Biomedical Services, Sangji University, Wonju 26339, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaBeta-glucan (β-glucan) is a natural polysaccharide produced by fungi, bacteria, and plants. Although it has been reported that β-glucan enhances innate immune memory responses, it is unclear whether different types of β-glucans display similar immune effects. To address this issue, we employed zymosan (β-1,3-glycosidic linkage) and pustulan (β-1,6-glycosidic linkage) to investigate their in vivo effects on innate memory immune responses. We examined the changes of innate memory-related markers in macrophages and natural killer (NK) cells, two immune cell types that display innate memory characteristics, at two different time points (16 h and 7 days) after β-glucan stimulation. We found that short-term (16 h) zymosan treatment significantly induced macrophages to upregulate IL15 production and increased surface IL15Rα expression on NK cells. In addition, long-term (7 days) zymosan treatment significantly induced macrophages to upregulate the expression of innate memory-related markers (e.g., TNFα, HIF1α, and mTOR) and induced NK cells to express enhanced levels of KLRG1, known as an innate memory-like marker. Our results provide support that zymosan can be an effective adjuvant to promote innate memory immune responses, providing a bridge between innate and adaptive immune cells to enhance various immune responses such as those directed against tumors.https://www.mdpi.com/1420-3049/28/15/5779beta-glucanzymosanpustulannatural killer cellsmacrophages
spellingShingle Hyun Jung Park
Sung Won Lee
Yun Hoo Park
Tae-Cheol Kim
Sujin Lee
Seyeong Lee
Luc Van Kaer
Seokmann Hong
In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
Molecules
beta-glucan
zymosan
pustulan
natural killer cells
macrophages
title In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
title_full In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
title_fullStr In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
title_full_unstemmed In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
title_short In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice
title_sort in vivo zymosan treatment induces il15 secreting macrophages and klrg1 expressing nk cells in mice
topic beta-glucan
zymosan
pustulan
natural killer cells
macrophages
url https://www.mdpi.com/1420-3049/28/15/5779
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