Quantitative appraisal of murine filariasis confirms host strain differences but reveals that BALB/c females are more susceptible than males to Litomosoides sigmodontis

Quantitative appraisal of murine filariasis confirms host strain differences but reveals that BALB/c females are more susceptible than males to Litomosoides sigmodontis
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DOI:
10.1016/j.micinf.2004.12.019
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发表时间:
2005-04-01
影响因子:
5.8
通讯作者:
Allen, JE
Allen, JE
中科院分区:
医学3区
文献类型:
--
作者:
Graham, AL;Taylor, MD;Allen, JE

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Litomosoides sigmodontis是一种啮齿类丝虫,可感染近交系实验室小鼠,在BALB/c品系中完全发育至通畅。像C57 BL/6这样的菌株被认为是耐药性的,因为尽管丝虫可以发展,但从未检测到循环中的微丝蚴。该模型系统首次将小鼠免疫学的力量应用于有关丝虫感染易感性的基本问题。由于这是一个相对较新的模型,生物学的许多方面仍有待发现或更清楚地定义。我们对85个实验进行了主要分析,以定量评估在整个感染过程中雄性与雌性以及BALB/c与C57 BL/6小鼠中丝虫存活和繁殖的差异。这个大数据集为以前的定性评价提供了有力的统计支持,包括观察到C57 BL/6小鼠的耐药表型早在感染后10天(dpi)就可检测到。然而,一个意想不到的发现是,与雌性小鼠相比,雄性BALB/c小鼠的丝虫存活率降低。雌性BALB/c小鼠的蠕虫回收率以及微丝蚴的患病率和密度均高于雄性BALB/c小鼠。因此,L. sigmodontis巴克斯了丝虫在男性中易感性增加的趋势。这可能部分地与成虫L.乙状结肠与淋巴丝虫有趣的是,BALB/c性别对微丝蚴血症的影响与虫数无关。总之,这项研究大大改善了我们对宿主-L的理解。sigmodontis的关系,并严重挑战了男性更容易受到丝虫感染的教条。(c)2005年,Elsevier SAS。All rights reserved.
Litomosoides sigmodontis, a rodent filarial nematode, can infect inbred laboratory mice, with full development to patency in the BALB/c strain. Strains such as C57BL/6 are considered resistant, because although filarial development can occur, circulating microfilariae are never detected. This model system has, for the first time, allowed the power of murine immunology to be applied to fundamental questions regarding susceptibility to filarial nematode infection. As this is a relatively new model, many aspects of the biology remain to be discovered or more clearly defined. We undertook a major analysis of 85 experiments, to quantitatively assess differences in filarial survival and reproduction in male versus female and BALB/c versus C57BL/6 mice over the full course of infection. This large dataset provided hard statistical support for previous qualitative reviews, including observations that the resistant phenotype of C57BL/6 mice is detectable as early as 10 days postinfection (dpi). An unexpected finding, however, was that filarial survival was reduced in male BALB/c mice compared to their female counterparts. Worm recovery as well as the prevalence and density of microfilariae were higher in female compared with male BALB/c mice. Therefore, L. sigmodontis bucks the filarial trend of increased susceptibility in males. This could be partially explained by the different anatomical locations of adult L. sigmodontis versus lymphatic filariae. Interestingly, the effects of BALB/c sex upon microfilaremia were independent of worm number. In summary, this study has significantly refined our understanding of the host-L. sigmodontis relationship and, critically, has challenged the dogma that males are more susceptible to filarial infection. (c) 2005 Elsevier SAS. All rights reserved.