Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection

被引:85
作者
Di Liberto, Diana [1 ]
Locati, Massimo [2 ,3 ]
Caccamo, Nadia [1 ]
Vecchi, Annunciata [2 ]
Meraviglia, Serena [1 ]
Salerno, Alfredo [1 ]
Sireci, Guido [1 ]
Nebuloni, Manuela [4 ]
Caceres, Neus [5 ,6 ]
Cardona, Pere-Joan [5 ,6 ]
Dieli, Francesco [1 ]
Mantovani, Alberto [2 ,3 ]
机构
[1] Univ Palermo, Dipartimento Biopatol & Metodol Biomed, I-90134 Palermo, Italy
[2] IRCCS, Ist Clin Humanitas, I-20089 Rozzano, Italy
[3] Univ Milan, L Sacco Inst Med Sci, Ist Patol Gen, I-20133 Milan, Italy
[4] Univ Milan, L Sacco Inst Med Sci, Pathol Unit, I-20133 Milan, Italy
[5] Univ Autonoma Barcelona, Badalona 08916, Spain
[6] Fdn Inst Invest Ciencies Salut Germans Trias i Puj, Unitat TB Expt, Dept Microbiol, I-90134 Palermo, Italy
关键词
D O I
10.1084/jem.20070608
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 1 beta, 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.
引用
收藏
页码:2075 / 2084
页数:10
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