美国国立卫生研究院Jesus G. Valenzuela等研究人员合作发现，利什曼原虫遗传交换由IgM自然抗体介导。相关论文于2023年10月25日在线发表在《自然》杂志上。
研究人员证明了天然IgM（IgMn）抗体通过诱导瞬时形成球形寄生虫团块，促进寄生虫融合和杂交形成，从而介导寄生虫基因交换。研究人员证实，来自无利什曼病动物的IgMn与利什曼寄生虫表面结合，诱导寄生虫转录本和蛋白质的表达发生显著变化。尽管寄生虫表面磷聚糖（包括脂磷聚糖）而非IgMn诱导寄生虫凝集所需的，但经过糖苷酶处理后，利什曼原虫与IgMn的结合部分消失。值得注意的是，寄生虫团块的短暂形成对于利什曼原虫体外杂交至关重要。
在体内，研究人员观察到，与对照组相比，沙蝇在摄入含有IgMn的第二份血餐后，杂交形成率增加了12倍。此外，只有在提供IgMn的沙蝇中才能观察到杂交种和亲本系交配产生的重组后代。体外和体内IgM诱导的利什曼原虫杂交都产生了全基因组杂交种，这些杂交种显示出相同的双亲贡献模式。利什曼原虫利用宿主的天然抗体促进昆虫载体的交配，这建立了寄生虫-宿主-载体相互依存的新范例，其通过促进基因交换来提高寄生虫的多样性和适应性。
据了解，介导利什曼原虫遗传交换的宿主因素尚未明确。
附：英文原文
Title: Leishmania genetic exchange is mediated by IgM natural antibodies
Author: Serafim, Tiago D., Iniguez, Eva, Barletta, Ana Beatriz F., Cecilio, Pedro, Doehl, Johannes S. P., Short, Mara, Lack, Justin, Nair, Vinod, Disotuar, Maria, Wilson, Timothy, Coutinho-Abreu, Iliano V., Meneses, Claudio, Andersen, John, Alves E Silva, Thiago Luiz, Oliveira, Fabiano, Vega-Rodriguez, Joel, Barillas-Mury, Carolina, Ribeiro, Jos M. C., Beverley, Stephen M., Kamhawi, Shaden, Valenzuela, Jesus G.
Issue&Volume: 2023-10-25
Abstract: Host factors that mediate Leishmania genetic exchange are not well defined. Here we demonstrate that natural IgM (IgMn)1,2,3,4 antibodies mediate parasite genetic exchange by inducing the transient formation of a spherical parasite clump that promotes parasite fusion and hybrid formation. We establish that IgMn from Leishmania-free animals binds to the surface of Leishmania parasites to induce significant changes in the expression of parasite transcripts and proteins. Leishmania binding to IgMn is partially lost after glycosidase treatment, although parasite surface phosphoglycans, including lipophosphoglycan, are not required for IgMn-induced parasite clumping. Notably, the transient formation of parasite clumps is essential for Leishmania hybridization in vitro. In vivo, we observed a 12-fold increase in hybrid formation in sand flies provided a second blood meal containing IgMn compared with controls. Furthermore, the generation of recombinant progeny from mating hybrids and parental lines were only observed in sand flies provided with IgMn. Both in vitro and in vivo IgM-induced Leishmania crosses resulted in full genome hybrids that show equal patterns of biparental contribution. Leishmania co-option of a host natural antibody to facilitate mating in the insect vector establishes a new paradigm of parasite–host–vector interdependence that contributes to parasite diversity and fitness by promoting genetic exchange.
DOI: 10.1038/s41586-023-06655-8
Source: https://www.nature.com/articles/s41586-023-06655-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
