Tissue Macrophages Suppress Viral Replication and Prevent Severe Immunopathology in an Interferon-I-Dependent Manner in Mice

被引：76

作者：

Lang, Philipp A. ^{[1
,2
]}

Recher, Mike ^{[1
]}

Honke, Nadine ^{[3
]}

Scheu, Stefanie ^{[4
]}

Borkens, Stephanie ^{[4
]}

Gailus, Nicole ^{[3
]}

Krings, Caroline ^{[3
]}

Meryk, Andreas ^{[3
]}

Kulawik, Andreas ^{[3
]}

Cervantes-Barragan, Luisa ^{[5
]}

Van Rooijen, Nico ^{[6
]}

Kalinke, Ulrich ^{[7
,9
]}

Ludewig, Burkhard ^{[5
]}

Hengartner, Hans ^{[1
]}

Harris, Nicola ^{[8
]}

Haeussinger, Dieter ^{[3
]}

Ohashi, Pamela S. ^{[2
]}

Zinkernagel, Rolf M. ^{[1
]}

Lang, Karl S. ^{[1
,3
]}

机构：

[1] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland

[2] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada

[3] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany

[4] Univ Dusseldorf, Inst Med Microbiol & Hosp Hyg, D-40225 Dusseldorf, Germany

[5] Kantonal Hosp, Inst Immunobiol, St Gallen, Switzerland

[6] Vrije Univ Amsterdam, Dept Mol Cell Biol, Amsterdam, Netherlands

[7] Ctr Expt & Clin Infect Res, TWINCORE, Hannover, Germany

[8] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Swiss Vaccine Res Inst, Global Hlth Inst, CH-1015 Lausanne, Switzerland

[9] Inst Expt Infect Res, Hannover, Germany

来源：

HEPATOLOGY | 2010年 / 52卷 / 01期

基金：

瑞士国家科学基金会; 加拿大健康研究院;

关键词：

HEPATITIS-C VIRUS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MONONUCLEAR PHAGOCYTE SYSTEM; HUMAN KUPFFER CELLS; ENDOTHELIAL-CELLS; B-VIRUS; IMMUNOHISTOCHEMICAL LOCALIZATION; DENDRITIC CELLS; HBV INFECTION; MARGINAL ZONE;

D O I：

10.1002/hep.23640

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

The innate immune response plays an essential role in the prevention of early viral dissemination. We used the lymphocytic choriomeningitis virus model system to analyze the role of tissue macrophages/Kupffer cells in this process. Our findings demonstrated that Kupffer cells are essential for the efficient capture of infectious virus and for preventing viral replication. The latter process involved activation of Kupffer cells by interferon (IFN)-I and prevented viral spread to neighboring hepatocytes. In the absence of Kupffer cells, hepatocytes were not able to suppress virus replication, even in the presence of IFN-I, leading to prolonged viral replication and severe T cell-dependent immunopathology. Conclusion: Tissue-resident macrophages play a crucial role in early viral capture and represent the major liver cell type exhibiting responsiveness to IFN-I and providing control of viral replication. (HEPATOLOGY 2010;52:25-32)

引用

页码：25 / 32

页数：8

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