Babu S, Porte P, Klei T R, Shultz L D, Rajan T V
Department of Pathology, University of Connecticut Health Center, Farmington 06030, USA.
J Immunol. 1998 Aug 1;161(3):1428-32.
Human lymphatic filariasis, which afflicts an estimated 120 million people worldwide, is caused by the large nematode parasites Wuchereria bancrofti and Brugia malayi. Filarial nematodes require both an arthropod vector and a mammalian host to complete their life cycle. Within the definitive (mammalian) host, the lymphatic filarial parasites reside in the lymph nodes and lymphatics, a seemingly hostile environment for infectious agents, since the location exposes them to the immune defenses of the host. We present data here that suggest that the growth of B. malayi in the mammalian host is dependent on host NK cell function. Comparisons of worm survival and development in different strains of mice with varying levels of NK cell activity reveal that NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice (with diminished to absent NK cell activity respectively), are nonpermissive to worm growth, while C.B-17-scid/scid mice with normal NK cell activity are highly permissive. Depletion of NK cells in the permissive C57BL/6J-scid/scid mice renders them nonpermissive to B. malayi growth, whereas stimulation of NK cells in NOD/LtSz-scid/scid mice makes them permissive. Tg epsilon26 mice, which lack NK and T cells, are nonpermissive, but, when reconstituted with NK cells by adoptive transfer of bone marrow cells from C57BL16J-scid/scid mice, are rendered permissive. This requirement for NK cell activity may explain the site specificity of these parasites. Furthermore, these data suggest that the interaction of the host immune system with the filarial parasite is double edged, with both host protective and parasite growth-promoting activities emanating from the former.
人类淋巴丝虫病在全球约有1.2亿人受累，由大型线虫寄生虫班氏吴策线虫和马来布鲁线虫引起。丝虫线虫需要节肢动物媒介和哺乳动物宿主来完成其生命周期。在终末（哺乳动物）宿主体内，淋巴丝虫寄生虫寄居于淋巴结和淋巴管中，这对感染因子来说似乎是一个充满敌意的环境，因为这个位置使它们暴露于宿主的免疫防御之下。我们在此展示的数据表明，马来布鲁线虫在哺乳动物宿主体内的生长依赖于宿主自然杀伤（NK）细胞的功能。对不同NK细胞活性水平的小鼠品系中线虫存活和发育情况的比较显示，NOD/LtSz-scid/scid和NOD/LtSz-scid/scid B2m（缺失）小鼠（分别具有减弱至缺失的NK细胞活性）不允许线虫生长，而具有正常NK细胞活性的C.B-17-scid/scid小鼠则高度允许线虫生长。在允许线虫生长的C57BL/6J-scid/scid小鼠中去除NK细胞会使其不允许马来布鲁线虫生长，而在NOD/LtSz-scid/scid小鼠中刺激NK细胞则会使其允许线虫生长。缺乏NK细胞和T细胞的Tg epsilon26小鼠不允许线虫生长，但是，当通过从C57BL16J-scid/scid小鼠过继转移骨髓细胞用NK细胞进行重建时，它们就变得允许线虫生长了。对NK细胞活性的这种需求可能解释了这些寄生虫的位点特异性。此外，这些数据表明宿主免疫系统与丝虫寄生虫的相互作用是双刃剑，前者既有宿主保护活性又有促进寄生虫生长的活性。
