Temporal delay of peak T-cell immunity determines Chlamydia pneumoniae pulmonary disease in mice.
Temporal delay of peak T-cell immunity determines Chlamydia pneumoniae pulmonary disease in mice.
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T 细胞免疫峰值的时间延迟决定了小鼠肺炎衣原体肺部疾病。
DOI：
10.1128/iai.00569-08
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发表时间：
2008
影响因子：
3.1
通讯作者：
Kaltenboeck,Bernhard
中科院分区：
文献类型：
--
作者：
Wang,Chengming;vanGinkel,FrederikW;Kim,Teayoun;Li,Dan;Li,Yihang;Dennis,JohnC;Kaltenboeck,Bernhard
严重衣原体疾病通常发生在既往感染后，由超敏反应引起，这也是消除衣原体所需的。在这里，我们通过具有四个二分效应的多变量建模定量分析了对肺炎衣原体重复感染的免疫和疾病反应：小鼠品系（A/J或C57 BL/6），膳食蛋白质含量（14%蛋白质和0.3%L-半胱氨酸-0.9%L-精氨酸，或24%蛋白质和0.5%L-半胱氨酸-2.0%L-精氨酸），膳食抗氧化剂含量（90 IU α-生育酚/kg体重与450 IU α-生育酚/kg和0.1% gl-ascorbate）和时间进程（感染后3或10天）。鼻内注射C.肺炎激发后，低蛋白/低抗氧化剂饮食的C57 BL/6小鼠，而不是其他饮食的C57 BL/6小鼠或A/J小鼠，在第3天表现出严重抑制的早期肺部炎症和泛T细胞（CD 3 δ+）和辅助T细胞（CD 45）反应，但后来在第10天严重加重了疾病。对比分析表明，重度C。肺炎是一种迟发型超敏反应（DTH），伴有肺巨噬细胞和Th 1细胞标志物转录物增加、Th 1：Th 2比值增加和Th 1细胞因子驱动的炎症。DTH、酶联免疫斑点和免疫组化荧光测定的功能分析结果与转录分析获得的结果一致。因此，继发性感染后的衣原体疾病是T细胞应答的暂时失调，其特征在于严重延迟的T辅助细胞应答，导致未能消除病原体并引发后来的病理性Th 1炎症。这种延迟的T细胞反应受宿主遗传控制和营养影响。时间和数量调节宿主T细胞群的机制是衣原体发病机制的关键决定因素。
Severe chlamydial disease typically occurs after previous infections and results from a hypersensitivity response that is also required for chlamydial elimination. Here, we quantitatively dissected the immune and disease responses to repeatedChlamydia pneumoniaelung infection by multivariate modeling with four dichotomous effects: mouse strain (A/J or C57BL/6), dietary protein content (14% protein and 0.3%l-cysteine-0.9%l-arginine, or 24% protein and 0.5%l-cysteine-2.0%l-arginine), dietary antioxidant content (90 IU α-tocopherol/kg body weight versus 450 IU α-tocopherol/kg and 0.1% gl-ascorbate), and time course (3 or 10 days postinfection). Following intranasalC. pneumoniaechallenge, C57BL/6 mice on a low-protein/low-antioxidant diet, but not C57BL/6 mice on other diets or A/J mice, exhibited profoundly suppressed early lung inflammatory and pan-T-cell (CD3δ+) and helper T-cell (CD45) responses on day 3 but later strongly exacerbated disease on day 10. Contrast analyses characterized severeC. pneumoniaedisease as being a delayed-type hypersensitivity (DTH) response with increased lung macrophage and Th1 cell marker transcripts, increased Th1:Th2 ratios, and Th1 cytokine-driven inflammation. Results from functional analyses by DTH, enzyme-linked immunospot, and immunohistofluorescence assays were consistent with the results obtained by transcript analysis. Thus, chlamydial disease after secondary infection is a temporal dysregulation of the T-cell response characterized by a profoundly delayed T-helper cell response that results in a failure to eliminate the pathogen and provokes later pathological Th1 inflammation. This delayed T-cell response is under host genetic control and nutritional influence. The mechanism that temporally and quantitatively regulates the host T-cell population is the critical determinant in chlamydial pathogenesis.