Wang Jingwen, Wu Yineng, Yang Guangxiao, Aksoy Serap
Department of Epidemiology of Microbial Diseases, Yale School of Public Heath, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12133-8. doi: 10.1073/pnas.0901226106. Epub 2009 Jul 8.
Tsetse flies, the sole vectors of African trypanosomes, have coevolved with mutualistic endosymbiont Wigglesworthia glossinidiae. Elimination of Wigglesworthia renders tsetse sterile and increases their trypanosome infection susceptibility. We show that a tsetse peptidoglycan recognition protein (PGRP-LB) is crucial for symbiotic tolerance and trypanosome infection processes. Tsetse pgrp-lb is expressed in the Wigglesworthia-harboring organ (bacteriome) in the midgut, and its level of expression correlates with symbiont numbers. Adult tsetse cured of Wigglesworthia infections have significantly lower pgrp-lb levels than corresponding normal adults. RNA interference (RNAi)-mediated depletion of pgrp-lb results in the activation of the immune deficiency (IMD) signaling pathway and leads to the synthesis of antimicrobial peptides (AMPs), which decrease Wigglesworthia density. Depletion of pgrp-lb also increases the host's susceptibility to trypanosome infections. Finally, parasitized adults have significantly lower pgrp-lb levels than flies, which have successfully eliminated trypanosome infections. When both PGRP-LB and IMD immunity pathway functions are blocked, flies become unusually susceptible to parasitism. Based on the presence of conserved amidase domains, tsetse PGRP-LB may scavenge the peptidoglycan (PGN) released by Wigglesworthia and prevent the activation of symbiont-damaging host immune responses. In addition, tsetse PGRP-LB may have an anti-protozoal activity that confers parasite resistance. The symbiotic adaptations and the limited exposure of tsetse to foreign microbes may have led to the considerable differences in pgrp-lb expression and regulation noted in tsetse from that of closely related Drosophila. A dynamic interplay between Wigglesworthia and host immunity apparently is influential in tsetse's ability to transmit trypanosomes.
采采蝇是非洲锥虫的唯一传播媒介，它与共生内共生菌舌蝇格氏菌共同进化。去除格氏菌会使采采蝇不育，并增加它们对锥虫感染的易感性。我们发现采采蝇肽聚糖识别蛋白（PGRP-LB）对于共生耐受和锥虫感染过程至关重要。采采蝇pgrp-lb在中肠中容纳格氏菌的器官（菌瘤）中表达，其表达水平与共生菌数量相关。清除格氏菌感染的成年采采蝇的pgrp-lb水平明显低于相应的正常成年采采蝇。RNA干扰（RNAi）介导的pgrp-lb缺失会导致免疫缺陷（IMD）信号通路的激活，并导致抗菌肽（AMP）的合成，从而降低格氏菌的密度。pgrp-lb的缺失还会增加宿主对锥虫感染的易感性。最后，被寄生的成年采采蝇的pgrp-lb水平明显低于成功清除锥虫感染的采采蝇。当PGRP-LB和IMD免疫途径功能都被阻断时，采采蝇对寄生变得异常敏感。基于保守酰胺酶结构域的存在，采采蝇PGRP-LB可能清除格氏菌释放的肽聚糖（PGN），并防止激活破坏共生菌的宿主免疫反应。此外，采采蝇PGRP-LB可能具有抗原生动物活性，赋予寄生虫抗性。采采蝇的共生适应以及它们对外来微生物的有限接触可能导致了采采蝇与密切相关的果蝇在pgrp-lb表达和调控方面的显著差异。格氏菌与宿主免疫之间动态的相互作用显然对采采蝇传播锥虫的能力有影响。
