Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells

Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells
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DOI:
10.1128/iai.73.8.4522-4529.2005
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发表时间:
2005-08-01
影响因子:
3.1
通讯作者:
Houpt, E
Houpt, E
中科院分区:
医学2区
文献类型:
--
作者:
Asgharpour, A;Gilchrist, C;Houpt, E

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溶组织内阿米巴肠道感染的建立取决于小鼠品系; C57 BL/6小鼠高度耐药,C3 H/HeJ小鼠相对易感。我们发现,肠道感染的抵抗力是独立的淋巴细胞活性或H-2单倍型,并发生在第一个小时到天后的挑战,根据体内成像。在18 h后的挑战,耐药C57 BL/6小鼠盲肠组织学上不显着,在敏感的C3 H/HeJ小鼠中观察到严重的炎症。C3 H/HeJ和C57 BL/6小鼠盲肠基因表达的比较表明,有寄生虫诱导的促炎和中性粒细胞趋化性转录上调,并有下调的转化生长因子0信号分子。地塞米松预处理通过先天的、淋巴细胞非依赖性机制消除了C3 H/HeJ或CBA小鼠的部分抵抗,但对C57 BL/6小鼠的高水平抵抗没有影响。类似地,与对照抗体处理的小鼠相比,施用嗜中性粒细胞消耗性抗Gr-1单克隆抗体(RB 6 - 8 C5)降低了CBA小鼠的部分抗性,并导致严重的病理学,但对C57 BL/6抗性没有影响。这些数据表明,存在对E.与其他报道相反,这表明中性粒细胞在肠道阿米巴病中具有保护作用,而不是破坏性的。
Establishment of intestinal infection with Entamoeba histolytica depends on the mouse strain; C57BL/6 mice are highly resistant, and C3H/HeJ mice are relatively susceptible. We found that resistance to intestinal infection was independent of lymphocyte activity or H-2 haplotype and occurred in the first hours to days postchallenge according to in vivo imaging. At 18 h postchallenge, the ceca of resistant C57BL/6 mice were histologically unremarkable, in contrast to the severe inflammation observed in susceptible C3H/HeJ mice. Comparison of cecal gene expression in C3H/HeJ and C57BL/6 mice demonstrated that there was parasite-induced upregulation of proinflammatory and neutrophil chemotaxis transcripts and there was downregulation of transforming growth factor 0 signaling molecules. Pretreatment with dexamethasone abrogated the partial resistance of C3H/HeJ or CBA mice through an innate, lymphocyte-independent mechanism, but it had no effect on the high-level resistance of C57BL/6 mice. Similarly, administration of a neutrophil-depleting anti-Gr-1 monoclonal antibody (RB6-8C5) decreased the partial resistance of CBA mice and led to severe pathology compared to control antibody-treated mice, but it had no effect on C57BL/6 resistance. These data indicate that there are discrete mechanisms of innate resistance to E. histolytica depending on the host background and, in contrast to other reports, imply that neutrophils are protective and not damaging in intestinal amebiasis.