IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages
Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the...
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doaj-d2411c77451b4bd0a9547e07984920d82020-11-25T01:40:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00270450974IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in MacrophagesMin-Jung Kang0Ah-Ra Jang1Ji-Yeon Park2Jae-Hun Ahn3Tae-Sung Lee4Dong-Yeon Kim5Moo-Seung Lee6Seungwoo Hwang7Yu-Jin Jeong8Jong-Hwan Park9Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaKorean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaLaboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaInterleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after A. baumannii infection, compared to WT mice. Intranasal administration of recombinant IL-10 rescued mice from the lethality of the bacterial infection by promoting bacterial clearance and reducing production of cytokines and chemokines in the lungs. In vitro experiments revealed that IL-10 enhanced phagocytosis and bacterial killing by macrophages by upregulating the macrophage receptor with collagenous structure (MARCO). In addition, A. baumannii-induced activation of STAT3 was impaired in IL-10-deficient macrophages, which was essential for expression of MARCO. Intranasal adoptive transfer of WT macrophages resulted in significant increases in mice survival and bacterial clearance in IL-10-deficient mice infected with A. baumannii. Our results show that IL-10 played an important role in the host defense against pulmonary infection of A. baumannii by promoting the antibacterial function of macrophages by regulating MARCO expression through the STAT3-mediated pathway.https://www.frontiersin.org/article/10.3389/fimmu.2020.00270/fullAcinetobacter baumanniiinterleukin-10macrophagesmacrophage receptor with collagenous structureSTAT3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Min-Jung Kang Ah-Ra Jang Ji-Yeon Park Jae-Hun Ahn Tae-Sung Lee Dong-Yeon Kim Moo-Seung Lee Seungwoo Hwang Yu-Jin Jeong Jong-Hwan Park |
spellingShingle |
Min-Jung Kang Ah-Ra Jang Ji-Yeon Park Jae-Hun Ahn Tae-Sung Lee Dong-Yeon Kim Moo-Seung Lee Seungwoo Hwang Yu-Jin Jeong Jong-Hwan Park IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages Frontiers in Immunology Acinetobacter baumannii interleukin-10 macrophages macrophage receptor with collagenous structure STAT3 |
author_facet |
Min-Jung Kang Ah-Ra Jang Ji-Yeon Park Jae-Hun Ahn Tae-Sung Lee Dong-Yeon Kim Moo-Seung Lee Seungwoo Hwang Yu-Jin Jeong Jong-Hwan Park |
author_sort |
Min-Jung Kang |
title |
IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages |
title_short |
IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages |
title_full |
IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages |
title_fullStr |
IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages |
title_full_unstemmed |
IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages |
title_sort |
il-10 protects mice from the lung infection of acinetobacter baumannii and contributes to bacterial clearance by regulating stat3-mediated marco expression in macrophages |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-02-01 |
description |
Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after A. baumannii infection, compared to WT mice. Intranasal administration of recombinant IL-10 rescued mice from the lethality of the bacterial infection by promoting bacterial clearance and reducing production of cytokines and chemokines in the lungs. In vitro experiments revealed that IL-10 enhanced phagocytosis and bacterial killing by macrophages by upregulating the macrophage receptor with collagenous structure (MARCO). In addition, A. baumannii-induced activation of STAT3 was impaired in IL-10-deficient macrophages, which was essential for expression of MARCO. Intranasal adoptive transfer of WT macrophages resulted in significant increases in mice survival and bacterial clearance in IL-10-deficient mice infected with A. baumannii. Our results show that IL-10 played an important role in the host defense against pulmonary infection of A. baumannii by promoting the antibacterial function of macrophages by regulating MARCO expression through the STAT3-mediated pathway. |
topic |
Acinetobacter baumannii interleukin-10 macrophages macrophage receptor with collagenous structure STAT3 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00270/full |
work_keys_str_mv |
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