The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies.
The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies.
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DOI：
10.1371/journal.ppat.1005744
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发表时间：
2016-07
期刊：
影响因子：
6.7
通讯作者：
Van Den Abbeele J
中科院分区：
文献类型：
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作者：
Caljon G;Van Reet N;De Trez C;Vermeersch M;Pérez-Morga D;Van Den Abbeele J
采采蝇是引起昏睡病的布氏锥虫寄生虫的唯一媒介。目前，我们对感染的亚循环形式与哺乳动物宿主皮肤之间的早期界面的了解非常有限。本研究利用染有荧光标记的布氏体寄生虫的莫氏舌蝇在小鼠中引发自然感染。超环锥虫通过皮内途径具有高度传染性，与锥虫的血流途径形成鲜明对比。寄生虫从真皮接种部位迁移，导致18小时内引流淋巴结和42小时内外周血中可检测到寄生虫水平。一部分寄生虫留在真皮中并积极增殖。通过与不同标记的寄生虫开始混合感染，皮肤寄生虫明确显示来自最初的接种，而不是来自血液循环的再次入侵。扫描电镜显示，这些寄生在皮肤上的寄生虫与结缔组织中的脂肪细胞之间存在复杂的相互作用，通过脂肪细胞周围网状纤维缠绕，并嵌入胶原束之间。实验传播实验结合血食蝇的分子寄生虫检测证明，真皮锥虫可在初次传播后立即从接种部位获得。高分辨率热成像也显示，皮内寄生虫扩张引起皮肤表面温度升高。总的来说，真皮代表了高传染性的超环锥虫的传递部位，宿主从真皮中被系统定植，在真皮中，增殖亚群仍然受到与脂肪细胞和胶原纤维结构复杂相互作用的物理限制。昏睡病是由锥虫引起的，锥虫通过吸血的采采蝇传播。本研究用荧光标记的寄生虫在小鼠中建立了一个实验传播模型，使我们能够研究采采蝇叮咬自然传播后的命运。在哺乳动物皮肤中接种后，发现在采采蝇唾液腺中产生的寄生虫具有高度传染性，这与先前从血液中纯化的锥虫的观察结果形成了对比。这项研究揭示了一部分寄生虫保留在皮肤中，并在最初接种部位附近积极增殖，导致皮肤温度显着升高。这种滞留与脂肪细胞和胶原纤维结构的相互作用有关。实验传播实验能够证明，寄生虫在最初传播后可立即从接种地点获得。
Tsetse flies are the sole vectors of Trypanosoma brucei parasites that cause sleeping sickness. Our knowledge on the early interface between the infective metacyclic forms and the mammalian host skin is currently highly limited. Glossina morsitans flies infected with fluorescently tagged T. brucei parasites were used in this study to initiate natural infections in mice. Metacyclic trypanosomes were found to be highly infectious through the intradermal route in sharp contrast with blood stream form trypanosomes. Parasite emigration from the dermal inoculation site resulted in detectable parasite levels in the draining lymph nodes within 18 hours and in the peripheral blood within 42 h. A subset of parasites remained and actively proliferated in the dermis. By initiating mixed infections with differentially labeled parasites, dermal parasites were unequivocally shown to arise from the initial inoculum and not from a re-invasion from the blood circulation. Scanning electron microscopy demonstrated intricate interactions of these skin-residing parasites with adipocytes in the connective tissue, entanglement by reticular fibers of the periadipocytic baskets and embedment between collagen bundles. Experimental transmission experiments combined with molecular parasite detection in blood fed flies provided evidence that dermal trypanosomes can be acquired from the inoculation site immediately after the initial transmission. High resolution thermographic imaging also revealed that intradermal parasite expansion induces elevated skin surface temperatures. Collectively, the dermis represents a delivery site of the highly infective metacyclic trypanosomes from which the host is systemically colonized and where a proliferative subpopulation remains that is physically constrained by intricate interactions with adipocytes and collagen fibrous structures. Sleeping sickness is caused by trypanosomes that are transmitted by the blood feeding tsetse flies. The present study has established an experimental transmission model with fluorescently labeled parasites in mice that allows us to study their fate following natural transmission by a tsetse fly bite. Parasites that arise in the tsetse salivary glands were found to be highly infective following inoculation in the mammalian skin in contrast with previous observations made for trypanosomes purified from the blood stream. This study unveiled that a proportion of parasites is retained in the skin and actively proliferates close to the initial inoculation site resulting in significantly elevated skin temperatures. This retention was linked to interaction with fat cells and collagen fibrous structures. Experimental transmission experiments were able to demonstrate that parasites can be acquired from the inoculation site immediately after the initial transmission.