Levast Benoît, Hogan Daniel, van Kessel Jill, Strom Stacy, Walker Stew, Zhu Jianzhong, Meurens François, Gerdts Volker
Vaccine and Infectious Disease Organization-International Vaccine Centre, University of Saskatchewan, Saskatoon, SK, Canada.
Department of Computer Science, University of Saskatchewan, Saskatoon, SK, Canada.
Front Vet Sci. 2019 Jul 12;6:233. doi: 10.3389/fvets.2019.00233. eCollection 2019.
Host defense peptides (HDPs) show both antimicrobial and immunomodulatory properties making them important mediators of the host immune system. In humans but also in pigs many HDPs have been identified and important families such as cathelicidins and defensins have been established. In our study, we assessed: (i) the potential interactions that could occur between three peptides (LL37, PR39, and synthetic innate defense regulator (IDR)-1002) and a common TLR ligand called poly(I:C); (ii) the impact of selected peptides on the response of alveolar macrophage (AM) to poly(I:C) stimulation; (iii) the anti-porcine respiratory and reproductive syndrome virus (PRRSV) properties of the peptides; and (iv) their adjuvant potential in a PRRSV challenge experiment after immunization with different vaccine formulations. The results are as following: LL37, PR39, and IDR-1002 were able to interact with poly(I:C) using an agarose gel migration assay. Then, an alteration of AM's response to poly(I:C) stimulation was observed when the cells were co-stimulated with LL37 and IDR-1002. Regarding the anti-PRRSV potential of the peptides only LL37 showed a PRRSV inhibition in infected AM as well as precision cut lung slices (PCLS). However, in our conditions and despite their immunomodulatory properties, neither LL37 nor IDR-1002 showed any convincing potential as an adjuvant when associated to killed PRRSV in a challenge experiment. In conclusion, both antiviral and immunomodulatory properties could be identified for LL37, only immunomodulatory properties for IDR-1002, and both peptides failed to improve the immune response consecutive to an immunization with a killed vaccine in a PPRSV challenge experiment. However, further studies are needed to fully decipher and explain differences between peptide properties.
宿主防御肽（HDPs）具有抗菌和免疫调节特性，使其成为宿主免疫系统的重要介质。在人类以及猪体内，已鉴定出许多HDPs，并建立了诸如cathelicidins和防御素等重要家族。在我们的研究中，我们评估了：（i）三种肽（LL37、PR39和合成的固有防御调节剂（IDR）-1002）与一种名为聚肌胞苷酸（poly(I:C)）的常见Toll样受体（TLR）配体之间可能发生的相互作用；（ii）所选肽对肺泡巨噬细胞（AM）对聚肌胞苷酸刺激反应的影响；（iii）这些肽的抗猪繁殖与呼吸综合征病毒（PRRSV）特性；以及（iv）在用不同疫苗制剂免疫后，它们在PRRSV攻毒实验中的佐剂潜力。结果如下：使用琼脂糖凝胶迁移试验发现LL37、PR39和IDR-1002能够与聚肌胞苷酸相互作用。然后，当细胞与LL37和IDR-1002共同刺激时，观察到AM对聚肌胞苷酸刺激的反应发生了改变。关于这些肽的抗PRRSV潜力，只有LL37在感染的AM以及精密切割肺切片（PCLS）中显示出PRRSV抑制作用。然而，在我们的实验条件下，尽管它们具有免疫调节特性，但在攻毒实验中，当与灭活的PRRSV联合使用时，LL37和IDR-1002都没有显示出任何令人信服的佐剂潜力。总之，LL37具有抗病毒和免疫调节特性，IDR-1002仅具有免疫调节特性，并且在PPRSV攻毒实验中，这两种肽都未能改善灭活疫苗免疫后的免疫反应。然而，需要进一步研究来全面解读和解释肽特性之间的差异。
