Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among Different Tsetse Species.
Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among Different Tsetse Species.
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DOI：
10.1371/journal.pntd.0004038
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发表时间：
2015
影响因子：
3.8
通讯作者：
Aksoy S
中科院分区：
文献类型：
--
作者：
Zhao X;Alves e Silva TL;Cronin L;Savage AF;O'Neill M;Nerima B;Okedi LM;Aksoy S
采采症是致病性锥虫的媒介，是非洲人和动物锥虫病的病原体。采采子唾液的成分(唾液体)在摄血过程中被引入哺乳动物的寄主叮咬部位，对采采子有效取食的能力非常重要，但也可以影响疾病传播，并作为宿主暴露的生物标志物。我们比较了两个亚属的四个采采种的唾液体成分：Morsitans亚属：Glossina morsitans morsitans(GMM)和Glossina pallidipe(GPD)，Palpalis亚属：GPG和Glossina fuscipes(GFF)，并用免疫印迹法评估了它们的免疫原性和血清交叉反应。同一亚属不同种蝇唾液酸组分的蛋白质和免疫谱具有较大的相似性和交叉反应性。从非洲疾病流行地区获得的牛的血清显示出反映采采症种类分布的免疫原性概况。我们用LC-MS/MS分析了GMM唾液酸组分，确定TAg5、Tsal1/Tsal2和Sgp3是主要的免疫原性蛋白，5‘-核苷酸酶家族和腺苷脱氨酶生长因子(ADGF)家族的4个成员是主要的非免疫原性蛋白。在ADGF家族中，我们发现了四个密切相关的蛋白(TSGF-1、TSGF-2、ADGF-3和ADGF-4)，它们都在采采腺中表达。我们描述了采采树物种特有的表达谱和这些蛋白质的基因组定位。采用被动免疫的方法，评价了重组人TSGF(TSGF-1和TSGF-2)多克隆抗体对采采期适合度参数的影响。对循环中有抗TSGF抗体的小鼠进行有限的采采赛，会对它们的血液摄取能力造成轻微的损害，表现为消化不良、体重增加和总脂肪储备减少，尽管这些结果在统计学上没有显著意义。采采蝇对ADGF蛋白家族抗体的长期暴露研究是有必要的，以评估这个保守的家族在苍蝇生物学中的作用。昆虫唾液中含有许多蛋白质，它们在吸血过程中被注入哺乳动物的宿主体内。唾液蛋白增强昆虫的血液摄取能力，但它们也可以诱导哺乳动物的免疫反应，从而抑制成功的摄食，或者调节叮咬部位，以利于病原体的传播。在这里，我们研究了属于两个遥远物种组的四个不同采采族的唾液。我们发现，不同物种群体的唾液蛋白图谱是不同的。被蝇叮咬的实验小鼠对丰富的唾液蛋白表现出不同的免疫反应，不同采采种共享的唾液蛋白的抗原性也不同。我们发现，腺苷脱氨酶基序的ADGF家族中的一个成员TSGF-2在小鼠的Glossina morsitans中是非免疫原性的，而来自Glossina fuscipes的相同蛋白是高度免疫原性的。这种物种特异性免疫反应可被用作田间寄主暴露的生物标记物。我们还表明，短期暴露于由抗TSGF抗体被动免疫的小鼠中，会导致轻微的、但在统计学上没有显著的负面适应效应。因此，未来对非抗原性唾液蛋白的研究是有必要的，因为它们可以导致新的哺乳动物疫苗靶标，以减少现场的采采热种群。
Tsetse are vectors of pathogenic trypanosomes, agents of human and animal trypanosomiasis in Africa. Components of tsetse saliva (sialome) are introduced into the mammalian host bite site during the blood feeding process and are important for tsetse’s ability to feed efficiently, but can also influence disease transmission and serve as biomarkers for host exposure. We compared the sialome components from four tsetse species in two subgenera: subgenus Morsitans: Glossina morsitans morsitans (Gmm) and Glossina pallidipes (Gpd), and subgenus Palpalis: Glossina palpalis gambiensis (Gpg) and Glossina fuscipes fuscipes (Gff), and evaluated their immunogenicity and serological cross reactivity by an immunoblot approach utilizing antibodies from experimental mice challenged with uninfected flies. The protein and immune profiles of sialome components varied with fly species in the same subgenus displaying greater similarity and cross reactivity. Sera obtained from cattle from disease endemic areas of Africa displayed an immunogenicity profile reflective of tsetse species distribution. We analyzed the sialome fractions of Gmm by LC-MS/MS, and identified TAg5, Tsal1/Tsal2, and Sgp3 as major immunogenic proteins, and the 5'-nucleotidase family as well as four members of the Adenosine Deaminase Growth Factor (ADGF) family as the major non-immunogenic proteins. Within the ADGF family, we identified four closely related proteins (TSGF-1, TSGF-2, ADGF-3 and ADGF-4), all of which are expressed in tsetse salivary glands. We describe the tsetse species-specific expression profiles and genomic localization of these proteins. Using a passive-immunity approach, we evaluated the effects of rec-TSGF (TSGF-1 and TSGF-2) polyclonal antibodies on tsetse fitness parameters. Limited exposure of tsetse to mice with circulating anti-TSGF antibodies resulted in a slight detriment to their blood feeding ability as reflected by compromised digestion, lower weight gain and less total lipid reserves although these results were not statistically significant. Long-term exposure studies of tsetse flies to antibodies corresponding to the ADGF family of proteins are warranted to evaluate the role of this conserved family in fly biology. Insect saliva contains many proteins that are injected into the mammalian host during the blood feeding process. Saliva proteins enhance the blood feeding ability of insects, but they can also induce mammalian immune responses that inhibit successful feeding, or modulate the bite site to benefit pathogen transmission. Here we studied saliva from four different tsetse species that belong to two distant species groups. We show that the saliva protein profiles of different species groups vary. Experimental mice subjected to fly bites display varying immunological responses against the abundant saliva proteins and the antigenicity of the shared saliva proteins in different tsetse species differs. We show that one member of the ADGF family with adenosine deaminase motifs, TSGF-2, is non-immunogenic in Glossina morsitans in mice, while the same protein from Glossina fuscipes is highly immunogenic. Such species-specific immune responses could be exploited as biomarkers of host exposures in the field. We also show that short-term exposure of G. morsitans to mice passively immunized by anti-TSGF antibodies leads to slight but not statistically significant negative fitness effects. Thus, future investigations with non-antigenic saliva proteins are warranted as they can lead to novel mammalian vaccine targets to reduce tsetse populations in the field.
影响因子：
3.8
作者：
Caljon G;Duguma R;De Deken R;Schauvliege S;Gasthuys F;Duchateau L;Van Den Abbeele J
通讯作者：
Van Den Abbeele J