Shannon Jeffrey G, Howe Dale, Heinzen Robert A
Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8722-7. doi: 10.1073/pnas.0501863102. Epub 2005 Jun 6.
Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of the zoonotic disease Q fever. Acute human Q fever is characterized by flu-like symptoms that, in some cases, can result in a persistent infection that may reactivate months or years after initial exposure. Mechanisms by which this obligate parasite evades clearance by the host immune response during persistent infection are unknown. Here, we characterized the interaction of C. burnetii with dendritic cells (DC), critical components of both innate and adaptive immunity. Human DC were infected with two isogenic C. burnetii strains that differ in LPS length. Infection by the Nine Mile phase I (NMI) strain, which is fully virulent and produces full-length LPS, did not result in DC maturation. In contrast, infection by the avirulent Nine Mile phase II strain, producing a severely truncated LPS, resulted in toll-like receptor 4-independent DC maturation and approximately 10-fold more IL-12 and TNF production. NMI did not actively inhibit DC maturation as NMI-infected DC subsequently matured if treated with Escherichia coli LPS or Nine Mile phase II. Furthermore, removal of LPS from NMI dramatically increased its ability to stimulate DC. We propose a model whereby LPS of virulent C. burnetii masks toll-like receptor ligands from innate immune recognition by DC, thereby allowing replication without significant maturation or inflammatory cytokine production. This immune evasion strategy may allow C. burnetii to persist in an immunocompetent host.
伯氏考克斯体是一种专性细胞内细菌，也是人畜共患病Q热的病原体。人类急性Q热的特征是类似流感的症状，在某些情况下，可能导致持续性感染，这种感染可能在初次接触数月或数年后再次激活。在持续性感染期间，这种专性寄生虫逃避宿主免疫反应清除的机制尚不清楚。在此，我们描述了伯氏考克斯体与树突状细胞（DC）的相互作用，树突状细胞是固有免疫和适应性免疫的关键组成部分。用两种脂多糖（LPS）长度不同的同基因伯氏考克斯体菌株感染人类DC。完全有毒力且产生全长LPS的九里I期（NMI）菌株感染不会导致DC成熟。相比之下，产生严重截短LPS的无毒力九里II期菌株感染会导致不依赖Toll样受体4的DC成熟，且IL-12和TNF的产生量增加约10倍。NMI不会主动抑制DC成熟，因为如果用大肠杆菌LPS或九里II期处理，NMI感染的DC随后会成熟。此外，从NMI中去除LPS会显著增强其刺激DC的能力。我们提出了一个模型，即有毒力的伯氏考克斯体的LPS掩盖了DC对Toll样受体配体的固有免疫识别，从而允许其在不发生显著成熟或产生炎性细胞因子的情况下进行复制。这种免疫逃避策略可能使伯氏考克斯体在免疫功能正常的宿主体内持续存在。
