Background Scrub typhus, caused by Orientia tsutsugamushi, involves infiltration of a mixture of perivascular lymphocytes and macrophages into affected organs. We investigated if this is characterized by chemokine dysregulation. Methods mRNA expression of chemokines and receptors was screened in whole blood by cDNA microarray in a subgroup of patients and controls. Regulated transcripts were analyzed in plasma by enzyme immunoassays (chemokines) and in whole blood by quantitative polymerase chain reaction (receptors) from patients with scrub typhus (n = 129), patients with similar febrile illness without O tsutsugamushi infection (n = 31), and healthy controls (n = 31). Results cDNA microarray identified dysregulation of the chemokines CCL18 and CCL23 and the receptor CCR3 in severe scrub typhus. Plasma CCL7 (a ligand for CCR3), CCL18, and CCL23 were higher in patients with scrub typhus, with a decline during follow-up. Conversely, mRNA levels of CCR3 and CCR8 (the receptor for CCL18) were decreased in whole blood at hospital admission, followed by an increase during follow-up. CCL7 was independently associated with disease severity. Admission CCL7 levels were associated with short-time mortality. Conclusions Our findings suggest that CCL7 could represent a hitherto unknown pathogenic mediator in O tsutsugamushi infection, contributing to local and systemic inflammation.

中文翻译：

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Scrub 斑疹伤寒患者的 C-C 基序配体 7 和 C-C 基序趋化因子受体 3 失调及其与死亡率的相关性


背景 由恙虫 Orientia tsugamushi 引起的 擦洗 斑疹伤寒涉及血管周围淋巴细胞和巨噬细胞的混合物浸润到受影响的器官中。我们调查了这是否以趋化因子失调为特征。方法 通过患者和对照组的 cDNA 微阵列筛选全血中趋化因子和受体的 mRNA 表达。通过酶免疫测定 （趋化因子） 分析血浆中受控的转录物，并通过定量聚合酶链反应 （受体） 分析来自丛林斑疹伤寒患者 （n = 129）、无 O tsutsugamushi 感染的类似发热性疾病患者 （n = 31） 和健康对照者 （n = 31）。结果 cDNA 微阵列芯片鉴定了严重丛林斑疹伤寒中趋化因子 CCL18 和 CCL23 以及受体 CCR3 的失调。恙虫病患者的血浆 CCL7 （CCR3 的配体） 、 CCL18 和 CCL23 较高，随访期间下降。相反，入院时全血中 CCR3 和 CCR8 （CCL18 受体） 的 mRNA 水平降低，随后在随访期间升高。CCL7 与疾病严重程度独立相关。入院 CCL7 水平与短时死亡率相关。结论 我们的研究结果表明，CCL7 可能代表 O tsutsugamushi 感染中迄今为止未知的致病介质，导致局部和全身炎症。