Meier Cole J, Ahmed Shabbir, Estévez-Lao Tania Y, Hillyer Julián F
Department of Biological Sciences, Vanderbilt University, VU Station B 35-16342, Nashville, TN, 37235, USA.
Cell Tissue Res. 2025 Sep 19. doi: 10.1007/s00441-025-04011-y.
Infection induces the aggregation of hemocytes on the dorsal vessel of mosquitoes. These hemocytes, called periostial hemocytes, phagocytose pathogens and produce immune factors on the abdominal portion of the dorsal vessel, called the heart. One of these immune factors, nitric oxide, is a pleiotropic free radical that is an antimicrobial and a heartbeat reducer. But nitric oxide is not just produced by hemocytes. It is also synthesized by pericardial cells that flank the heart, and other tissues. To determine whether it is the periostial hemocytes or the pericardial cells that modulate the heart following infection, we chemically ablated the hemocytes using clodronate liposomes and measured immune responses and heart physiology. We demonstrate that clodronate liposomes ablate the sessile hemocytes, including the periostial hemocytes, while leaving the pericardial cells and heart integrity unaffected. Moreover, ablating hemocytes abolishes the phagocytosis of bacteria, alters the deposition of melanized bacteria, and decreases nitric oxide synthase activity on the heart. Importantly, hemocyte ablation eliminates the infection induced reduction of the heart rate, mainly by modifying the anterograde heart rate. Therefore, periostial hemocytes drive immune responses on the heart and infection-induced changes to circulatory physiology.
感染会诱导血细胞聚集在蚊子的背血管上。这些血细胞被称为围心膜血细胞，它们吞噬病原体并在背血管的腹部（即心脏）产生免疫因子。其中一种免疫因子一氧化氮是一种多效自由基，具有抗菌作用且能降低心跳。但一氧化氮并非仅由血细胞产生。它也由位于心脏两侧的心包细胞以及其他组织合成。为了确定感染后是围心膜血细胞还是心包细胞调节心脏，我们使用氯膦酸脂质体化学消融血细胞，并测量免疫反应和心脏生理功能。我们证明氯膦酸脂质体可消融固着血细胞，包括围心膜血细胞，同时不影响心包细胞和心脏的完整性。此外，消融血细胞会消除细菌的吞噬作用，改变黑化细菌的沉积，并降低心脏上一氧化氮合酶的活性。重要的是，血细胞消融消除了感染诱导的心率降低，主要是通过改变顺行心率实现的。因此，围心膜血细胞驱动心脏上的免疫反应以及感染诱导的循环生理变化。
