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¹ Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, 90134 Palermo, Italy
² Istituto Clinico Humanitas IRCCS, 20089 Rozzano, Italy
³ Istituto di Patologia Generale and ⁴ Pathology Unit, L. Sacco Institute of Medical Sciences, University of Milan, 20133 Milan, Italy
⁵ Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol and Universitat Autònoma de Barcelona, 08916 Badalona, Spain

CORRESPONDENCE Francesco Dieli: dieli{at}unipa.it

D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6^–/– mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor , interleukin 1β, and interferon ) in bronchoalveolar lavage and serum. High levels of inflammatory cytokines in D6^–/– infected mice were associated with liver and kidney damage, resulting in both liver and renal failure. Blocking inflammatory CC chemokines with a cocktail of antibodies reversed the inflammatory phenotype of D6^–/– mice but led to less controlled growth of M. tuberculosis. Thus, the D6 decoy receptor plays a key role in setting the balance between antimicrobial resistance, immune activation, and inflammation in M. tuberculosis infection.

D. Di Liberto and M. Locati contributed equally to this paper.

© 2008 Di Liberto 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.jem.org/misc/terms.shtml). 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/).

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