English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The adaptor molecule CARD9 is essential for tuberculosis control

Dorhoi, A., Desel, C., Yeremeev, V., Pradl, L., Brinkmann, V., Mollenkopf, H. J., et al. (2010). The adaptor molecule CARD9 is essential for tuberculosis control. Journal of Experimental Medicine, 207(4), 777-792.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : J. Exp. Med.

Files

show Files
hide Files
:
J_Exp_Med_2010_207_777.pdf (Publisher version), 4MB
Name:
J_Exp_Med_2010_207_777.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2010 Dorhoi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
License:
-

Locators

show

Creators

show
hide
 Creators:
Dorhoi, Anca1, Author              
Desel, Christiane1, Author              
Yeremeev, Vladimir2, Author
Pradl, Lydia1, Author              
Brinkmann, Volker3, Author              
Mollenkopf, Hans J.4, Author              
Hanke, Karin1, Author              
Gross, Olaf, Author
Ruland, Jürgen, Author
Kaufmann, Stefan H. E.1, Author              
Affiliations:
1Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664146              
2Max Planck Society, ou_persistent13              
3Core Facilities / Microscopy, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664142              
4Core Facilities / Microarray, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664141              

Content

show
hide
Free keywords: -
 Abstract: The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9(-/-) mice succumbed early after aerosol infection, with higher mycobacterial burden, pyogranulomatous pneumonia, accelerated granulocyte recruitment, and higher abundance of proinflammatory cytokines and granulocyte colony-stimulating factor (G-CSF) in serum and lung. Neutralization of G-CSF and neutrophil depletion significantly prolonged survival, indicating that an exacerbated systemic inflammatory disease triggered lethality of Card9(-/-) mice. CARD9 deficiency had no apparent effect on T cell responses, but a marked impact on the hematopoietic compartment. Card9(-/-) ranulocytes failed to produce IL-10 after Mycobaterium tuberculosis infection, suggesting that an absent antiinflammatory feedback loop accounted for granulocyte-dominated pathology, uncontrolled bacterial replication, and, ultimately, death of infected Card9(-/-) mice. Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis.

Details

show
hide
Language(s): eng - English
 Dates: 2010-04-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 533092
ISI: 000276552700011
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Experimental Medicine
  Alternative Title : J. Exp. Med.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 207 (4) Sequence Number: - Start / End Page: 777 - 792 Identifier: ISSN: 0022-1007