Tetsutani Kohhei, Ishiwata Kenji, Ishida Hidekazu, Tu Liping, Torii Motomi, Hamano Shinjiro, Himeno Kunisuke, Hisaeda Hajime
Department of Parasitology, Kyushu University Graduate School of Medical Science, Fukuoka 812-0054, Japan.
Eur J Immunol. 2009 Oct;39(10):2822-30. doi: 10.1002/eji.200939433.
Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. Co-infection with Hp led to reduced Py-responsive proliferation and IFN-gamma production of spleen cells, and higher activation of CD4(+)CD25(+)Foxp3(+) Treg. In vivo depletion of Treg recovered anti-Py immunity and rescued co-infected mice from exacerbated malaria. However, we did not observe any obvious ex vivo activation of Treg by either Hp products or living worms. Our results suggest that intestinal nematodes moderate host immune responses during acute malaria infection by aggressive activation of Treg. Elucidation of the mechanisms of Treg activation in situ is a target for future analyses.
疟疾和肠道线虫感染广泛存在，且常发生共感染。我们研究了共感染的肠道线虫是否会调节对共存疟原虫的免疫力。用约氏疟原虫17XNL（Py）感染C57BL/6小鼠是短暂且自限性的，但在感染小鼠肠道线虫多枝单睾线虫（Hp）之前感染Py会加重疟疾，导致更高的寄生虫负荷和小鼠存活率降低。与Hp共感染导致脾脏细胞对Py的反应性增殖和IFN-γ产生减少，以及CD4(+)CD25(+)Foxp3(+)调节性T细胞（Treg）的更高激活。体内去除Treg可恢复抗Py免疫力，并使共感染小鼠从加重的疟疾中获救。然而，我们未观察到Hp产物或活虫对Treg有任何明显的体外激活作用。我们的结果表明，肠道线虫在急性疟疾感染期间通过积极激活Treg来调节宿主免疫反应。阐明Treg原位激活机制是未来分析的目标。
