Weiss Shay, Levy Haim, Fisher Morly, Kobiler David, Altboum Zeev
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
Innate Immun. 2009 Feb;15(1):43-51. doi: 10.1177/1753425908100379.
The involvement of TLR2 receptor in the innate response to infection with Bacillus anthracis was investigated. We studied the response to virulent or attenuated Vollum strains in either in vitro assays using macrophage cultures, or in an in vivo model comparing the sensitivity of Syrian hamster cells (expressing normal TLR2) to Chinese hamster cells (lacking functional TLR2) to infection by the various B. anthracis strains. Phagocytosis experiments with murine cell cultures or primary macrophages from both hamster strains, using virulent or attenuated Tox(+)Cap(-), Tox(-)Cap(+) or Tox(-)Cap(-) spores indicated that the secretion of TNF-alpha was induced by all the bacterial spores and purified spore antigens. In contrast, capsular antigens induce secretion of TNF-alpha only by Syrian hamster macrophages indicating the involvement of a functional TLR2 in macrophage activation. Challenge experiments with both hamster strains by intranasal spore inoculation, indicated that, while both strains are equally sensitive to infection with the virulent strain, the Chinese hamster demonstrated a higher sensitivity to infection with the toxinogenic or encapsulated strains. In conclusion, our findings imply that TLR2 has an important role in the attempt of the innate immunity to control B. anthracis infection, although TNF-alpha secretion was found to be mediated by both TLR2-dependent and TLR2-independent pathways.
研究了Toll样受体2（TLR2）在炭疽芽孢杆菌感染固有免疫反应中的作用。我们在使用巨噬细胞培养物的体外试验中，或在一个体内模型中，比较叙利亚仓鼠细胞（表达正常TLR2）与中国仓鼠细胞（缺乏功能性TLR2）对各种炭疽芽孢杆菌菌株感染的敏感性，研究了对强毒株或减毒株Vollum菌株的反应。用来自两种仓鼠品系的鼠细胞培养物或原代巨噬细胞进行吞噬实验，使用强毒株或减毒株Tox(+)Cap(-)、Tox(-)Cap(+)或Tox(-)Cap(-)孢子，结果表明所有细菌孢子和纯化的孢子抗原均能诱导肿瘤坏死因子-α（TNF-α）的分泌。相比之下，荚膜抗原仅能诱导叙利亚仓鼠巨噬细胞分泌TNF-α，这表明功能性TLR2参与了巨噬细胞的激活。通过鼻内接种孢子对两种仓鼠品系进行攻毒实验，结果表明，虽然两种品系对强毒株感染的敏感性相同，但中国仓鼠对产毒或有荚膜菌株感染表现出更高的敏感性。总之，我们的研究结果表明，TLR2在固有免疫控制炭疽芽孢杆菌感染的过程中发挥重要作用，尽管发现TNF-α的分泌是由TLR2依赖和TLR2非依赖途径介导的。
