Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model

Acute otitis media (AOM) is one of the most common infectious diseases primarily caused by Streptococcus pneumoniae (S.pn) among children. Progranulin (PGRN) is a multifunctional growth factor widely expressed in various tissues and cells. Studies have confirmed that PGRN is involved in the developm...

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Egile Nagusiak: Zimeng Wang, Qian He, Xinxin Zhang, Yurong Ma, Fangmei Fan, Yilin Dong, Wenchun Xu, Yibing Yin, Yujuan He
Formatua: Artikulua
Hizkuntza:English
Argitaratua: Frontiers Media S.A. 2018-12-01
Saila:Frontiers in Immunology
Gaiak:
Sarrera elektronikoa:https://www.frontiersin.org/article/10.3389/fimmu.2018.02952/full
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author Zimeng Wang
Zimeng Wang
Qian He
Xinxin Zhang
Yurong Ma
Fangmei Fan
Yilin Dong
Wenchun Xu
Yibing Yin
Yujuan He
author_facet Zimeng Wang
Zimeng Wang
Qian He
Xinxin Zhang
Yurong Ma
Fangmei Fan
Yilin Dong
Wenchun Xu
Yibing Yin
Yujuan He
author_sort Zimeng Wang
collection DOAJ
description Acute otitis media (AOM) is one of the most common infectious diseases primarily caused by Streptococcus pneumoniae (S.pn) among children. Progranulin (PGRN) is a multifunctional growth factor widely expressed in various tissues and cells. Studies have confirmed that PGRN is involved in the development of a variety of inflammatory diseases. We found that the expression of PGRN increased significantly in the middle ear of wild mice with AOM. However, its physiological functions in AOM still remain unknown. To examine the role of PGRN during AOM, we established an acute otitis media model in both C57BL/6 wild mice and PGRN-deficient (PGRN−/−) mice via transbullar injection with S.pn clinical strain serotype 19F. Interestingly, we observed dual results: on one hand, macrophage recruitment notably increased in PGRN−/− mice compared with WT mice; on the other hand, the overall bacterial clearance was surprisingly dampened in PGRN−/− mice. The enhanced recruitment of macrophages was associated with increased production of chemokine (C-C motif) ligand 2 (CCL2), while the decreased bacterial clearance was associated with impaired endocytosis capacity of macrophages. The scavenging ability of bacteria in PGRN−/− mice was recovered with administration of recombinant PGRN. These results suggested a novel dual role of PGRN in affecting the activities of macrophages.
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spelling doaj.art-653559e15f7b46f7b5a81d0f5f7b33232022-12-22T01:03:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02952425771Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse ModelZimeng Wang0Zimeng Wang1Qian He2Xinxin Zhang3Yurong Ma4Fangmei Fan5Yilin Dong6Wenchun Xu7Yibing Yin8Yujuan He9Key Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Laboratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, ChinaAcute otitis media (AOM) is one of the most common infectious diseases primarily caused by Streptococcus pneumoniae (S.pn) among children. Progranulin (PGRN) is a multifunctional growth factor widely expressed in various tissues and cells. Studies have confirmed that PGRN is involved in the development of a variety of inflammatory diseases. We found that the expression of PGRN increased significantly in the middle ear of wild mice with AOM. However, its physiological functions in AOM still remain unknown. To examine the role of PGRN during AOM, we established an acute otitis media model in both C57BL/6 wild mice and PGRN-deficient (PGRN−/−) mice via transbullar injection with S.pn clinical strain serotype 19F. Interestingly, we observed dual results: on one hand, macrophage recruitment notably increased in PGRN−/− mice compared with WT mice; on the other hand, the overall bacterial clearance was surprisingly dampened in PGRN−/− mice. The enhanced recruitment of macrophages was associated with increased production of chemokine (C-C motif) ligand 2 (CCL2), while the decreased bacterial clearance was associated with impaired endocytosis capacity of macrophages. The scavenging ability of bacteria in PGRN−/− mice was recovered with administration of recombinant PGRN. These results suggested a novel dual role of PGRN in affecting the activities of macrophages.https://www.frontiersin.org/article/10.3389/fimmu.2018.02952/fullprogranulinStreptococcus pneumoniaeotitis mediachemokine (C-C motif) ligand 2phagocytosis
spellingShingle Zimeng Wang
Zimeng Wang
Qian He
Xinxin Zhang
Yurong Ma
Fangmei Fan
Yilin Dong
Wenchun Xu
Yibing Yin
Yujuan He
Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
Frontiers in Immunology
progranulin
Streptococcus pneumoniae
otitis media
chemokine (C-C motif) ligand 2
phagocytosis
title Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
title_full Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
title_fullStr Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
title_full_unstemmed Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
title_short Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model
title_sort innate anti microbial and anti chemotaxis properties of progranulin in an acute otitis media mouse model
topic progranulin
Streptococcus pneumoniae
otitis media
chemokine (C-C motif) ligand 2
phagocytosis
url https://www.frontiersin.org/article/10.3389/fimmu.2018.02952/full
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