Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells

Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells
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DOI:
10.1128/iai.00640-08
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发表时间:
2008-12-01
影响因子:
3.1
通讯作者:
DeRisi, Joseph L.
DeRisi, Joseph L.
中科院分区:
医学2区
文献类型:
--
作者:
Kim, Charles C.;Parikh, Sunil;DeRisi, Joseph L.

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为了更好地了解早期疟疾感染过程中的基因表达,我们对红细胞期夏氏疟原虫感染小鼠的早期血液反应进行了微阵列分析。感染后立即,我们观察到协调和顺序波的免疫反应,干扰素相关基因转录占主导地位的16小时感染后,其次是强烈增加自然杀伤(NK)细胞相关和主要组织相容性复合体I类相关的转录由32小时感染后。我们通过流式细胞术表明,观察到的NK细胞相关转录物的升高是感染期间血液中NK细胞比例急剧增加的结果。随后对从感染小鼠的外周血中分离的NK细胞的微阵列分析揭示了与NK细胞响应于感染而复制的观察一致的细胞增殖表达特征。在感染小鼠中采用过继转移细胞的研究中直接观察到NK细胞的早期增殖。这些数据表明,对夏氏疟原虫感染的血液的早期反应以干扰素的初级波为标志,随后是NK细胞的反应。
In order to gain a better understanding of gene expression during early malaria infection, we conducted microarray analysis of early blood responses in mice infected with erythrocytic-stage Plasmodium chabaudi. Immediately following infection, we observed coordinated and sequential waves of immune responses, with interferon-associated gene transcripts dominating by 16 h postinfection, followed by strong increases in natural killer (NK) cell-associated and major histocompatibility complex class I-related transcripts by 32 h postinfection. We showed by flow cytometry that the observed elevation in NK cell-associated transcripts was the result of a dramatic increase in the proportion of NK cells in the blood during infection. Subsequent microarray analysis of NK cells isolated from the peripheral blood of infected mice revealed a cell proliferation expression signature consistent with the observation that NK cells replicate in response to infection. Early proliferation of NK cells was directly observed in studies with adoptively transferred cells in infected mice. These data indicate that the early response to P. chabaudi infection of the blood is marked by a primary wave of interferon with a subsequent response by NK cells.