Concomitant experimental coinfection by Plasmodium berghei NK65-NY and Ascaris suum downregulates the Ascaris-specific immune response and potentiates Ascaris-associated lung pathology

Background: Ascariasis and malaria are highly prevalent parasitic diseases in tropical regions and often overlap in endemic areas, contributing to high morbidity and mortality rates in areas with poor sanitary conditions. Several studies have already aimed to correlate the effects of Ascaris-Plasmodium coinfections but obtained contradictory and inconclusive results. The present study investigated parasitological and immunopathological aspects of the lung in an experimental concomitant coinfection by Plasmodium berghei NK65-NY and Ascaris suum during larval ascariasis. Methods: C57BL/6J mice were inoculated with 1×104 P. berghei NK65-NY infected red blood cells (iRBCs) intraperitoneally and/or 2500 embryonated eggs of A. suum by oral gavage. P. berghei NK65-NY parasitemia, morbidity and survival rate were assessed. At the seventh day postinfection (dpi), A. suum lung burden, bronchoalveolar lavage (BAL), lung histopathological, lung cellular activity, hematological analysis and respiratory mechanics was performed. The concentrations of interleukin (IL)-1β, IL-12/IL-23p40, IL-6, IL-4, IL-33, IL-13, IL-5, IL-10, IL-17A, IFN-γ, TNF-α and TGF-β were assayed by sandwich ELISA. Results: P. berghei NK65-NY and A. suum coinfection results in Plasmodium-driven downregulation of the lung immune response that leads to an increase in larval migration, as evidenced by the decrease in larvae recovered in the lung parenchyma and increase in larvae recovered in the airways. This scenario conveys an intense airways hemorrhage and, consequently, the commitment of respiratory function that leads to high morbidity and early mortality. Conclusions: Our results suggest that this coinfection may potentiate Ascaris-associated pathology by the downmodulation of the Ascaris-specific immune response, resulting in the early death of affected animals.

背景：蛔虫病（Ascariasis）与疟疾是热带地区高流行的寄生虫病，二者常在流行区域重叠存在，在卫生条件恶劣的地区可造成极高的发病率与死亡率。已有多项研究尝试探究蛔虫-疟原虫共感染的相关影响，但所得结果相互矛盾且尚无定论。本研究针对伯氏疟原虫NK65-NY（Plasmodium berghei NK65-NY）与猪蛔虫（Ascaris suum）在幼虫移行期蛔虫病中的实验性共感染，开展肺部寄生虫学与免疫病理相关研究。
方法：将C57BL/6J小鼠经腹腔接种1×10⁴个感染伯氏疟原虫NK65-NY的红细胞（infected red blood cells, iRBCs），并/或经口灌胃2500枚猪蛔虫胚胎卵。本研究对伯氏疟原虫NK65-NY的虫血症水平、小鼠发病情况与存活率进行评估。于感染后第7天（days post infection, dpi），检测猪蛔虫肺部载虫量、支气管肺泡灌洗液（bronchoalveolar lavage, BAL）、肺部组织病理、肺部细胞活性、血液学分析以及呼吸力学指标。采用夹心酶联免疫吸附试验（sandwich ELISA）检测白细胞介素（interleukin, IL）-1β、IL-12/IL-23p40、IL-6、IL-4、IL-33、IL-13、IL-5、IL-10、IL-17A、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）以及转化生长因子β（TGF-β）的浓度。
结果：伯氏疟原虫NK65-NY与猪蛔虫共感染会引发疟原虫介导的肺部免疫应答下调，进而导致幼虫移行增加，具体表现为肺实质中回收的幼虫数量减少，而气道中回收的幼虫数量增多。该情况可引发严重的气道出血，并因此损害呼吸功能，最终导致高发病率与早期死亡。
结论：本研究结果表明，此种共感染可通过下调蛔虫特异性免疫应答，加重蛔虫相关病理损伤，导致受感染小鼠早期死亡。