The heparin-binding haemagglutinin of M-tuberculosis is required for extrapulmonary dissemination
The heparin-binding haemagglutinin of M-tuberculosis is required for extrapulmonary dissemination
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DOI：
10.1038/35084083
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发表时间：
2001-07-12
期刊：
影响因子：
64.8
通讯作者：
Menozzi, FD
中科院分区：
文献类型：
--
作者：
Pethe, K;Alonso, S;Menozzi, FD
结核病仍然是世界上由单一传染性病原体结核分枝杆菌造成的主要死亡原因，每年有300万人死亡，1000万新病例(1)。感染始于肺部，然后可迅速扩散到其他组织。结核分枝杆菌全基因组序列的可用性(3)和基因破坏技术的进步(4)导致了几个分枝杆菌决定因素参与毒力的鉴定（5-8）。然而，没有毒力因素具体参与肺外传播结核分枝杆菌已确定到目前为止。本研究表明，结核分枝杆菌或牛分枝杆菌编码肝素结合血凝素粘附素（hbhA）的hbhA基因的破坏显著影响分枝杆菌与上皮细胞的相互作用，但不影响与巨噬细胞样细胞的相互作用。当鼻腔给药小鼠时，突变株在脾脏定植中严重受损，但在肺定植中没有受损。用抗hbha抗体包膜野生型分枝杆菌也会在鼻内感染后阻碍传播。这些结果提供了证据，证明粘附素如HBHA是肺外传播所必需的，并且与非吞噬细胞的相互作用在结核病的发病机制中起重要作用。他们还表明，对HBHA的抗体反应可能会增加对结核病的免疫保护。
Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year(1). The infection initiates in the lungs and can then spread rapidly to other tissues(2). The availability of the entire M. tuberculosis genome sequence(3) and advances in gene disruption technologies(4) have led to the identification of several mycobacterial determinants involved in virulence(5-8). However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guerin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis.