Resistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16

被引：98

作者：

Conrady, C. D. ^{[1
]}

Zheng, M. ^{[2
]}

Fitzgerald, K. A. ^{[3
]}

Liu, C. ^{[4
]}

Carr, D. J. J. ^{[1
,2
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol, Oklahoma City, OK 73190 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA

[3] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA

[4] NYU, Sch Med, Dept Orthoped Surg & Cell Biol, New York, NY USA

来源：

MUCOSAL IMMUNOLOGY | 2012年 / 5卷 / 02期

关键词：

SIMPLEX-VIRUS ENCEPHALITIS; HUMAN CORNEAL; TLR3; DEFICIENCY; DENDRITIC CELLS; CYTOSOLIC DNA; IN-VIVO; ACTIVATION; EXPRESSION; PROTEIN; RECOGNITION;

D O I：

10.1038/mi.2011.63

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptors (TLRs) are innate sentinels required for clearance of bacterial and fungal infections of the cornea, but their role in viral immunity is currently unknown. We report that TLR signaling is expendable in herpes simplex virus (HSV)-1 containment as depicted by plaque assays of knockout mice (MyD88(-/-), Trif(-/-) and MyD88(-/-) Trif(-/-) double knockout) resembling wild-type controls. To identify the key sentinel in viral recognition of the cornea, in vivo knockdown of the DNA sensor IFI-16/p204 in the corneal epithelium was performed and resulted in a loss of IFN-regulatory factor-3 (IRF-3) nuclear translocation, interferon-alpha production, and viral containment. The sensor seems to have a similar function in other HSV clinically relevant sites such as the vaginal mucosa in which a loss of p204/IFI-16 results in significantly more HSV-2 shedding. Thus, we have identified an IRF-3-dependent, IRF-7- and TLR-independent innate sensor responsible for HSV containment at the site of acute infection.

引用

页码：173 / 183

页数：11

共 48 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].

Adachi, O ;

Kawai, T ;

Takeda, K ;

Matsumoto, M ;

Tsutsui, H ;

Sakagami, M ;

Nakanishi, K ;

Akira, S .

IMMUNITY, 1998, 9 (01) :143-150

[2] Distinctive roles for 2′,5′-oligoadenylate synthetases and double-stranded RNA-dependent protein kinase R in the in vivo antiviral effect of an adenoviral vector expressing murine IFN-β [J].

Al-Khatib, K ;

Williams, BRG ;

Silverman, RH ;

Halford, W ;

Carr, DJJ .

JOURNAL OF IMMUNOLOGY, 2004, 172 (09) :5638-5647

[3] Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection [J].

Austin, BA ;

James, C ;

Silverman, RH ;

Carr, DJJ .

JOURNAL OF IMMUNOLOGY, 2005, 175 (02) :1100-1106

[4] Herpes simplex virus encephalitis in human UNC-93B deficiency [J].

Casrouge, Armanda ;

Zhang, Shen-Ying ;

Eidenschenk, Celine ;

Jouanguy, Emmanuelle ;

Puel, Anne ;

Yang, Kun ;

Alcais, Alexandre ;

Picard, Capucine ;

Mahfoufi, Nora ;

Nicolas, Nathalie ;

Lorenzo, Lazaro ;

Plancoulaine, Sabine ;

Senechal, Brigitte ;

Geissmann, Frederic ;

Tabeta, Koichi ;

Hoebe, Kasper ;

Du, Xin ;

Miller, Richard L. ;

Heron, Benedicte ;

Mignot, Cyril ;

de Villemeur, Thierry Billette ;

Lebon, Pierre ;

Dulac, Olivier ;

Rozenberg, Flore ;

Beutler, Bruce ;

Tardieu, Marc ;

Abel, Laurent ;

Casanova, Jean-Laurent .

SCIENCE, 2006, 314 (5797) :308-312

[5] RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway [J].

Chiu, Yu-Hsin ;

MacMillan, John B. ;

Chen, Zhijian J. .

CELL, 2009, 138 (03) :576-591

[6] Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth [J].

Cho, Won Gil ;

Albuquerque, Romulo J. C. ;

Kleinman, Mark E. ;

Tarallo, Valeria ;

Greco, Adelaide ;

Nozaki, Miho ;

Green, Martha G. ;

Baffi, Judit Z. ;

Ambati, Balamurali K. ;

De Falco, Massimo ;

Alexander, Jonathan S. ;

Brunetti, Arturo ;

De Falco, Sandro ;

Ambati, Jayakrishna .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (17) :7137-7142

[7] A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes [J].

Conrady, Christopher D. ;

Jones, Heather ;

Zheng, Min ;

Carr, Daniel J. J. .

JOURNAL OF BIOMEDICAL RESEARCH, 2011, 25 (02) :111-119

[8] Loss of the Type I Interferon Pathway Increases Vulnerability of Mice to Genital Herpes Simplex Virus 2 Infection [J].

Conrady, Christopher D. ;

Halford, William P. ;

Carr, Daniel J. J. .

JOURNAL OF VIROLOGY, 2011, 85 (04) :1625-1633

[9] Herpes simplex type I (HSV-1) infection of the nervous system: Is an immune response a good thing? [J].

Conrady, Christopher D. ;

Drevets, Douglas A. ;

Carr, Daniel J. J. .

JOURNAL OF NEUROIMMUNOLOGY, 2010, 220 (1-2) :1-9

[10] Loss of Mandibular Lymph Node Integrity Is Associated with an Increase in Sensitivity to HSV-1 Infection in CD118-Deficient Mice [J].

Conrady, Christopher D. ;

Thapa, Manoj ;

Wuest, Todd ;

Carr, Daniel J. J. .

JOURNAL OF IMMUNOLOGY, 2009, 182 (06) :3678-3687

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