Artemisinin Research Center and Institute of Science and Technology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Parasitology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, China.
Parasit Vectors. 2020 Sep 3;13(1):440. doi: 10.1186/s13071-020-04309-6.
Although Plasmodium parasites and intestinal helminths share common endemic areas, the mechanisms of these co-infections on the host immune response remain not fully understood. Liver involvement in severe Plasmodium falciparum infections is a significant cause of morbidity and mortality. However, the effect of pre-existing Trichinella spiralis infection on the immune response and liver immune-pathogenesis in P. berghei ANKA (PbANKA)-infected mice needs to be elucidated.
Outbred Kunming mice were infected with T. spiralis and 9 days later were challenged with P. berghei ANKA (PbANKA), and the investigation occurred at 13 days after co-infection.
Compared with PbANKA-mono-infected mice, T. spiralis + PbANKA-co-infected mice had similar survival rate but lower PbANKA parasitaemia; however, there were more severe hepatosplenomegaly, increased liver and spleen indexes, and increased liver pathology observed by hematoxylin and eosin staining; higher expression levels of galectin (Gal)-1, Gal-3, CD68 macrophages, and elastase-positive neutrophils measured by immunohistochemical staining; upregulated mRNA expression levels of Gal-1, Gal-3, cytokines (interferon-gamma (IFNγ) and interleukin (IL)-6), and M1 macrophage polarization marker (inducible nitric oxide synthase (iNOS)) in the liver, and increased expression levels of Gal-1, IFNγ, IL-6, eosinophil cationic protein, eosinophil protein X, and M1 (IL-1β and iNOS) and M2 (Ym1) macrophage polarization markers in the spleen of co-infected mice detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). In vitro study showed that compared with PbANKA-mono-infected mice, there were significantly increased expression levels of Gal-1, Gal-3, IL-6, IL-1β, and iNOS in the peritoneal macrophage isolated from co-infected mice detected by using qRT-PCR. Correlation analysis revealed significant positive correlations between Gal-3 and IL-1β in the peritoneal macrophages isolated from PbANKA-mono-infected mice, between Gal-3 and IFNγ in the spleen of co-infected mice, and between Gal-1 and Ym1 in the peritoneal macrophages isolated from co-infected mice.
Our data indicate that pre-existing infection of T. spiralis may suppress P. berghei parasitaemia and aggravate malaria-induced liver pathology through stimulating Gal-1 and Gal-3 expression, activating macrophages, neutrophils, and eosinophils, and promoting mediator release and cytokine production.
疟原虫寄生虫和肠道蠕虫共同存在于流行地区，但这些合并感染对宿主免疫反应的机制尚不完全清楚。严重的恶性疟原虫感染导致肝脏受累，是发病率和死亡率的重要原因。然而，先前感染旋毛虫对伯氏疟原虫 ANKA（PbANKA）感染小鼠的免疫反应和肝脏免疫发病机制的影响仍需阐明。
对昆明种小鼠进行旋毛虫感染，9 天后用伯氏疟原虫 ANKA（PbANKA）进行攻虫，在合并感染后 13 天进行调查。
与 PbANKA 单感染组相比，旋毛虫+PbANKA 合并感染组的存活率相似，但疟原虫血症较低；然而，苏木精-伊红染色观察到更严重的肝脾肿大、肝脾指数增加和肝组织病理学改变；免疫组化染色显示半乳糖凝集素（Gal）-1、Gal-3、巨噬细胞 CD68 和弹性蛋白酶阳性中性粒细胞表达水平升高；肝组织中 Gal-1、Gal-3、细胞因子（干扰素-γ（IFNγ）和白细胞介素（IL）-6）和 M1 巨噬细胞极化标记物（诱导型一氧化氮合酶（iNOS））的 mRNA 表达水平上调，脾组织中 Gal-1、IFNγ、IL-6、嗜酸性粒细胞阳离子蛋白、嗜酸性粒细胞蛋白 X 和 M1（IL-1β 和 iNOS）和 M2（Ym1）巨噬细胞极化标记物的表达水平上调，实时定量逆转录聚合酶链反应（qRT-PCR）检测到的合并感染小鼠。体外研究表明，与 PbANKA 单感染组相比，qRT-PCR 检测到合并感染小鼠腹腔巨噬细胞中 Gal-1、Gal-3、IL-6、IL-1β 和 iNOS 的表达水平显著升高。相关性分析显示，PbANKA 单感染小鼠腹腔巨噬细胞中 Gal-3 与 IL-1β 之间存在显著正相关，合并感染小鼠脾组织中 Gal-3 与 IFNγ 之间以及合并感染小鼠腹腔巨噬细胞中 Gal-1 与 Ym1 之间存在显著正相关。
本研究数据表明，先前感染旋毛虫可能通过刺激 Gal-1 和 Gal-3 的表达，激活巨噬细胞、中性粒细胞和嗜酸性粒细胞，促进介质释放和细胞因子产生，抑制疟原虫血症并加重疟疾引起的肝组织病理学改变。
