Pickering Alison K, Osorio Manuel, Lee Gloria M, Grippe Vanessa K, Bray Mechelle, Merkel Tod J
Laboratory of Respiratory and Special Pathogens, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Infect Immun. 2004 Nov;72(11):6382-9. doi: 10.1128/IAI.72.11.6382-6389.2004.
Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential early step in the establishment of infection. This transfer is believed to occur by means of carriage within alveolar macrophages following phagocytosis. Therefore, the ability of B. anthracis to transit through the host macrophage or dendritic cell appears to be an early and critical step in B. anthracis pathogenesis. In this work, we examined the cytokine responses to spore infection in mouse primary peritoneal macrophages, in primary human dendritic cells, and during a spore aerosol infection model utilizing the susceptible A/J mouse strain. We demonstrated that both mouse peritoneal macrophages and human dendritic cells exhibited significant intracellular bactericidal activity during the first hours following uptake, providing the necessary time to mount a cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In addition to TNF-alpha and IL-6, human dendritic cells produced the cytokines IL-1beta, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera obtained from infected animals. In this study, we provide further evidence of an acute cytokine response when cells in culture and mice are infected with B. anthracis spores.
炭疽杆菌是炭疽病的病原体，是一种革兰氏阳性、形成芽孢的细菌。吸入性炭疽是最严重的形式，与疾病的快速进展相关，且结果往往是致命的。从呼吸道上皮转移至局部淋巴结似乎是感染确立过程中一个必不可少的早期步骤。据信这种转移是在吞噬作用后通过肺泡巨噬细胞内的携带作用而发生的。因此，炭疽杆菌穿过宿主巨噬细胞或树突状细胞的能力似乎是炭疽杆菌发病机制中的一个早期关键步骤。在这项研究中，我们检测了在小鼠原代腹腔巨噬细胞、原代人树突状细胞以及利用易感A/J小鼠品系的芽孢气溶胶感染模型中，对芽孢感染的细胞因子反应。我们证明，小鼠腹腔巨噬细胞和人树突状细胞在摄取后的最初几个小时内均表现出显著的细胞内杀菌活性，为在细胞裂解前产生细胞因子反应提供了必要时间。在小鼠腹腔巨噬细胞中观察到强烈的肿瘤坏死因子（TNF-α）和白细胞介素-6（IL-6）反应。除了TNF-α和IL-6外，人树突状细胞还产生细胞因子IL-1β、IL-8和IL-12。在从感染动物获得的血清中检测到Th1和Th2细胞因子的混合物。在本研究中，我们提供了进一步的证据，证明当培养细胞和小鼠感染炭疽杆菌芽孢时会出现急性细胞因子反应。
