The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.
The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.
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蚊子的中肠上皮调节细胞增殖和内复制以响应生理挑战。
DOI：
10.1186/s12915-023-01769-x
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发表时间：
2024-01-29
期刊：
影响因子：
5.4
通讯作者：
Buchon, N.
中科院分区：
文献类型：
--
作者：
Taracena-Agarwal, M. L.;Hixson, B.;Nandakumar, S.;Girard-Mejia, A. P.;Chen, R. Y.;Huot, L.;Padilla, N.;Buchon, N.
关键词：
吸血蚊子传播许多导致人类疾病的病原体。病原体的获得和传播发生在雌蚊吸血以获得繁殖所需的营养时。蚊子的中肠上皮是传染性病毒和寄生虫的进入点。我们研究了中肠上皮细胞的动力学在五个主要的蚊子载体物种，通过定量PH 3阳性细胞（有丝分裂增殖的指示），掺入核苷酸类似物（伴随增殖和/或内复制的DNA合成的指示），和倍性（流式细胞术）的成年女性后中肠上皮细胞群。我们的研究结果表明，上皮动态的出现后的成熟和成熟的糖喂养的肠道是相似的成员伊蚊，库蚊，和按蚊属。在出苗后的前三天，中肠后部感兴趣区域中约20%的细胞掺入核苷酸类似物，同时具有增殖活性和向更高倍性的广泛转变。在维持糖的成熟蚊子中，从羽化后5至8天，感兴趣的中肠后部区域中平均3.5%的细胞掺入核苷酸类似物，有丝分裂细胞的一致存在表明恒定的细胞更新。口腔细菌感染引发了有丝分裂和核苷酸类似物掺入的急剧增加，表明蚊子中肠经历了加速的细胞周转，以应对损害。最后，吸血导致细胞增殖增加，但反应的性质和强度因蚊子种类和血液来源（人、牛、禽或人工）而异。在安。冈比亚，肠上皮细胞似乎重新进入细胞周期，以增加倍性后，消耗血液从所有来源，除了禽。我们看到上皮细胞的增殖、分化和内复制重塑了以血液喂养的肠道，以增加倍性，可能是为了促进代谢活性的增加。我们的研究结果突出了蚊子对不同挑战的生理反应中中肠上皮的可塑性。在线版本包含补充材料，可通过10.1186/s12915-023-01769-x获得。
Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites. We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian. We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes’ physiological responses to distinct challenges. The online version contains supplementary material available at 10.1186/s12915-023-01769-x.
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