State Key Laboratory of Agrobiotechnology, Key Laboratory of Zoonosis of Ministry of Agriculture, National Animal Protozoa Laboratory and College of Veterinary Medicine, China Agricultural University, Beijing, China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Parasit Vectors. 2019 Apr 25;12(1):182. doi: 10.1186/s13071-019-3441-8.
Pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns and activate downstream signalling pathways, resulting in modulation of host immunity against pathogens. Here, we investigated whether PRR-mediated recognition is involved in host immune responses to the blood-feeding nematode Haemonchus contortus.
During blood-feeding, H. contortus secretes immune-modulating antigens into host blood. Therefore, we stimulated sheep peripheral blood mononuclear cells (PBMCs) with H. contortus soluble extract (HcAg) and performed transcriptional profiling.
HcAg upregulated two genetically linked CLRs (CLEC2L and KLRG2), two NLRs attenuating inflammation (NLRP12 and NLRC3) and one G protein-coupled receptor with potent anti-inflammatory effects (HCAR2). Furthermore, several Th2-related transcription factors (ATF3, IRF4, BCL3 and NFATC) were also upregulated, which may confer anti-inflammatory type 2 immune responses to HcAg.
Together, our preliminary studies provide new insights into how the host innate immune system controls type 2 immunity to H. contortus. Further work will be needed to identify H. contortus products recognized by the host innate immune system and determine the Th2 polarization ability of these putative PRR ligands.
模式识别受体(PRRs)可以识别病原体相关的分子模式,并激活下游信号通路,从而调节宿主对病原体的免疫反应。在这里,我们研究了 PRR 介导的识别是否参与宿主对吸血线虫捻转血矛线虫的免疫反应。
捻转血矛线虫在吸血时将免疫调节抗原分泌到宿主血液中。因此,我们用捻转血矛线虫可溶性提取物(HcAg)刺激绵羊外周血单核细胞(PBMCs)并进行转录谱分析。
HcAg 上调了两个遗传上相关的 CLRs(CLEC2L 和 KLRG2)、两个减轻炎症的 NLRs(NLRP12 和 NLRC3)和一个具有强大抗炎作用的 G 蛋白偶联受体(HCAR2)。此外,还上调了几个 Th2 相关转录因子(ATF3、IRF4、BCL3 和 NFATC),这可能赋予 HcAg 抗炎的 2 型免疫反应。
总之,我们的初步研究提供了新的见解,即宿主固有免疫系统如何控制对捻转血矛线虫的 2 型免疫反应。需要进一步研究来识别宿主固有免疫系统识别的捻转血矛线虫产物,并确定这些假定的 PRR 配体的 Th2 极化能力。