Chemokine Receptor 7 Is Essential for Coxiella burnetii Whole-Cell Vaccine-Induced Cellular Immunity but Dispensable for Vaccine-Mediated Protective Immunity
Chemokine Receptor 7 Is Essential for Coxiella burnetii Whole-Cell Vaccine-Induced Cellular Immunity but Dispensable for Vaccine-Mediated Protective Immunity
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DOI：
10.1093/infdis/jiz146
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发表时间：
2019-08-15
影响因子：
6.4
通讯作者：
Samuel, James E.
中科院分区：
文献类型：
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作者：
Chen, Chen;van Schaik, Erin J.;Samuel, James E.
背景针对贝氏柯克斯体感染的保护性免疫力通过接种强毒（PI-WCV）而非无毒力（PII-WCV）的全细胞灭活细菌来赋予。强毒和无毒C. Burnetii的脂多糖（LPS）分别为光滑脂多糖和粗糙脂多糖。用PI-WCV和PII-WCV接种小鼠。分别使用蛋白芯片微阵列和ELISpot评价体液和细胞应答。使用流式细胞术评估用PI-WVC和PII-WVC刺激后的树突状细胞（DC）成熟。通过疫苗攻毒试验验证了受体CCR 7的重要性。除了对PI-LPS的特异性抗体应答外，观察到类似的抗体谱，但用PI-WCV接种后IgG滴度显著更高。此外，在用PI-WCV免疫的小鼠中检测到更高频率的抗原特异性CD 4（+）T细胞。PI-WCV刺激的DC显示出显著更高的CCR 7水平和向次级淋巴器官的迁移能力。野生型和CCR 7缺陷小鼠的免疫保护研究证实，CCR 7对PI-WCV诱导的细胞免疫至关重要。PI-WVC刺激对C.通过刺激DC中的迁移行为来保护小鼠的细胞免疫。此外，对LPS的体液免疫应答是保护性免疫的重要组成部分。
Background. Protective immunity against Coxiella burnetii infection is conferred by vaccination with virulent (PI-WCV), but not avirulent (PII-WCV) whole-cell inactivated bacterium. The only well-characterized antigenic difference between virulent and avirulent C. burnetii is they have smooth and rough lipopolysaccharide (LPS), respectively.Methods. Mice were vaccinated with PI-WCV and PII-WCV. Humoral and cellular responses were evaluated using protein chip microarrays and ELISpots, respectively. Dendritic cell (DC) maturation after stimulation with PI-WVC and PII-WVC was evaluated using flow cytometry. Vaccine-challenge studies were performed to validate the importance of the receptor CCR7.Results. Other than specific antibody response to PI-LPS, similar antibody profiles were observed but IgG titers were significantly higher after vaccination with PI-WCV. Furthermore, higher frequency of antigen-specific CD4(+) T cells was detected in mice immunized with PI-WCV. PI-WCV-stimulated DCs displayed significantly higher levels of CCR7 and migratory ability to secondary lymphoid organs. Challenge-protection studies in wild-type and CCR7-deficient mice confirmed that CCR7 is critical for PI-WCV-induced cellular immunity.Conclusions. PI-WVC stimulates protective immunity to C. burnetii in mice through stimulation of migratory behavior in DCs for protective cellular immunity. Additionally, the humoral immune response to LPS is an important component of protective immunity.