title: Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection.
abstract: 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 alpha, interleukin 1beta, and interferon gamma) 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.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, 90134 Palermo, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Di Liberto
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Serena
authors.initials: S
authors.lastname: Meraviglia
authors.forename: Alfredo
authors.initials: A
authors.lastname: Salerno
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Neus
authors.initials: N
authors.lastname: Caceres
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D007107:Immune System; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010641:Phenotype; D054447:Receptors, CCR10 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097628:Chemokine Receptor D6
chemical_list: D000890:Anti-Infective Agents; D007371:Interferon-gamma; D053583:Interleukin-1beta; D054447:Receptors, CCR10; D014409:Tumor Necrosis Factor-alpha; D000097628:Chemokine Receptor D6