Laboratory of Host-Parasite Interaction Studies, ICMR-National Institute of Malaria Research, Dwarka, New Delhi, 110077, India.
Department of Biotechnology, Kumaun University, Nainital, Uttarakhand, India.
Immunol Cell Biol. 2020 Oct;98(9):757-769. doi: 10.1111/imcb.12374. Epub 2020 Aug 14.
The immune blood cells "hemocytes" of mosquitoes impart a highly selective immune response against various microorganisms/pathogens. Among several immune effectors, fibrinogen-related proteins (FREPs) have been recognized as key modulators of cellular immune responses; however, their physiological relevance has not been investigated in detail. Our ongoing comparative RNA-sequencing analysis identified a total of 13 FREPs originating from naïve sugar-fed, blood-fed, bacterial challenged and Plasmodium vivax-infected hemocytes in Anopheles stephensi. Transcriptional profiling of the selected seven FREP transcripts showed distinct responses against different pathophysiological conditions, where an exclusive induction of FREP12 after 10 days of P. vivax infection was observed. This represents a possible role of FREP12 in immunity against free circulating sporozoites and needs to be explored in the future. When challenged with live bacterial injection in the thorax, we observed a higher affinity of FREP13 and FREP65 toward Gram-negative and Gram-positive bacteria in the mosquito hemocytes, respectively. Furthermore, we observed increased bacterial survival and proliferation, which is likely compromised by the downregulation of TEP1, in FREP13 messenger RNA-depleted mosquito hemolymph. In contrast, after blood-feeding, we also noticed a significant delay of 24 h in the enrichment of gut endosymbionts in the FREP13-silenced mosquitoes. Taken together, we conclude that hemocyte-specific FREP13 carries the unique ability of tissue-specific regulation, having an antagonistic antibacterial role in the hemolymph, and an agonistic role against gut endosymbionts.
蚊子的免疫血细胞“hemocytes”对各种微生物/病原体赋予了高度选择性的免疫反应。在几种免疫效应物中，纤维蛋白原相关蛋白（FREPs）已被认为是细胞免疫反应的关键调节剂；然而，它们的生理相关性尚未得到详细研究。我们正在进行的比较 RNA 测序分析在幼稚的糖喂养、血液喂养、细菌挑战和恶性疟原虫感染的 Anopheles stephensi 血细胞中总共鉴定了 13 种源自 FREPs 的 FREPs。对选定的 7 种 FREP 转录本的转录谱分析显示，它们对不同的病理生理条件有明显的反应，在恶性疟原虫感染 10 天后观察到 FREP12 的特异性诱导。这代表了 FREP12 在针对游离循环子孢子的免疫中的可能作用，需要在未来进行探索。当在胸部用活细菌注射进行挑战时，我们观察到 FREP13 和 FREP65 在蚊子血细胞中对革兰氏阴性菌和革兰氏阳性菌分别具有更高的亲和力。此外，我们观察到细菌存活和增殖增加，这可能是由于 FREP13 信使 RNA 耗尽的蚊子血淋巴中 TEP1 的下调而受到损害。相比之下，在吸血后，我们还注意到 FREP13 沉默的蚊子中肠道共生菌的富集延迟了 24 小时。总之，我们得出结论，血细胞特异性 FREP13 具有组织特异性调节的独特能力，在血淋巴中具有拮抗的抗菌作用，并且对肠道共生菌具有激动作用。
