分枝杆菌感染中HBD-3及TLRs的调控机制研究

Tuberculosis, which is caused by infection with Mycobacterium tuberculosis (Mtb), remains one of the major bacterial infections worldwide. Innate immunity plays an important role in the host defense against M. tuberculosis. As effectors of innate immunity, antimicrobial peptides directly kill a broad spectrum of bacteria, fungi, and viruses. In addition, these peptides modify the local inflammatory response and activate mechanisms of adaptive immunity. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of M. tuberculosis, including Toll-like receptors (TLRs), among the TLR family, TLR2, TLR4, and TLR9 play the most prominent roles in the initiation of the immune response against tuberculosis. Several molecules, such as active vitamin D3，which is induced by TLR stimulation, have been shown to direct innate immune responses to mycobacteria. In our earlier study, HBD-3 was presumed to have relationship with the pathogenesis of mycobacterium skin infection..The aim of study will reveal the role of HBD-3 in cutaneous tuberculosis, and the regulation mechanism of VitD3, HBD-3 and TLRs in cutaneous Mycobacterium infection.

结核是由结核分枝杆菌(Mtb)感染引起的,目前仍然是全球主要的细菌感染。天然免疫在宿主防御结核分枝杆菌中发挥了重要作用。抗菌肽作为天然免疫的一部分具有广泛的直接杀死细菌、真菌、病毒的能力，不仅可以调节局部炎症反应并可激活获得性免疫。好几种模式识别受体(PPRs)参与了结核分枝杆菌的识别,其中包括Toll样受体(TLRs), 其中TLR2,TLR4,TLR9在人类抗结核菌感染的免疫反应起始阶段起到突出的作用。可以由Toll样受体刺激产生的活性维生素D3显示出可参与抗结核菌感染的先天免疫反应的调节。在我们前期研究中显示HBD-3在皮肤分枝杆菌感染的发病过程中更具相关性。本研究的目的是揭示HBD-3对皮肤结核分枝杆菌感染的作用，探索TLR2、4、9 和HBD-3以及活性维生素D3在皮肤结核分枝杆菌感染中的调控机制。

抗菌肽作为天然免疫的一部分具有广泛的直接杀死细菌、真菌、病毒的能力，不仅可以调节局部炎症反应并可激活获得性免疫，我们前期研究中显示HBD-3在皮肤分枝杆菌感染的发病过程中更具相关性。Toll样受体(TLRs)：其中TLR2,TLR4,TLR9在人类抗结核菌感染的免疫反应起始阶段起到突出的作用, 活性维生素D3显示出可参与抗结核菌感染的先天免疫反应的调节。.我们分别用RT-PCR，免疫组化和Western-blotting的方法，研究LL-37、HBD-2和HBD-3在皮肤结核及结核疹皮损中的表达。并用培养的人角质形成细胞系（HaCaT细胞），观察BCG-PPD刺激TLR2 ，TLR4 ，TLR9和HBD-3 mRNA和蛋白的表达；探讨维生素D3对BCG-PPD刺激角质形成细胞后TLR2，TLR4，TLR9和HBD-3表达的调控机制。.我们发现在皮肤结核和结核疹皮损中抗菌肽LL-37、HBD-2和HBD-3 mRNA及蛋白均有表达，均参与了皮肤结核和结核疹的免疫调节，但在皮肤结核和结核疹皮损中的表达并不完全一致，BCG-PPD刺激可上调人角质形成细胞系HaCaT细胞TLR2，TLR4和TLR9 mRNA和蛋白的表达；维生素D3可下调TLR2，TLR4和TLR9 mRNA和蛋白的表达；维生素D3可抑制TLR2，TLR4和TLR9的表达。提示维生素D3可抑制固有免疫的发生。