Laboratório de Imunologia Experimental, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
Laboratório de Mosquitos Geneticamente Modificados, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
Immunology. 2019 Sep;158(1):47-59. doi: 10.1111/imm.13096.
During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts' skin. In addition to the anti-haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non-sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non-sensitized and salivary gland extract- (SGE-)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE-sensitized mice than in non-sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non-sensitized and SGE-sensitized mice. When compared with steady-state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non-sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B-cells and CD4 T-cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva-dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.
在探测和吸血过程中，吸血蚊子将混合有唾液分子的混合物注入其脊椎动物宿主的皮肤中。除了抗凝血和免疫调节作用外，蚊子唾液还会引发急性炎症反应，尤其是在致敏宿主中。在这里，我们通过流式细胞术来描述 Aedes aegypti 蚊子叮咬在致敏和非致敏 BALB/c 小鼠皮肤中引起的水肿和细胞浸润。Ae. aegypti 叮咬会在非致敏和唾液腺提取物（SGE）致敏的小鼠的耳朵中引起水肿增加，分别在暴露后 6 小时和 24 小时达到峰值。对耳朵中总细胞数的定量表明，在 SGE 致敏的小鼠中，细胞募集比非致敏的小鼠更为强烈，组织学评估证实了这一发现。流式细胞术进行的免疫表型分析表明，蚊子叮咬能够在非致敏和 SGE 致敏的小鼠耳朵中的细胞群中产生复杂的变化。与稳定状态的耳朵相比，在非致敏和致敏的小鼠中，蚊子叮咬后明显募集到皮肤中的白细胞群是嗜酸性粒细胞、中性粒细胞、单核细胞、炎症性单核细胞、肥大细胞、B 细胞和 CD4 T 细胞，每一种都有其特定的动力学。细胞数量的绝对变化表明有两种细胞募集模式：（i）依赖唾液的迁移；（ii）依赖宿主免疫状态的迁移。这些发现表明，蚊子叮咬通过诱导依赖于宿主致敏程度的差异细胞迁移来影响皮肤微环境。
