Synthetic Cationic Peptide IDR-1002 and Human Cathelicidin LL37 Modulate the Cell Innate Response but Differentially Impact PRRSV Replication in vitro.

Benoît Levast,Jill Van Kessel,François Meurens,Stacy Strom,Volker Gerdts,Jianzhong Zhu,Stew Walker,Daniel Hogan

doi:10.3389/fvets.2019.00233

Benoît Levast, Jill Van Kessel + Show 6 more

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https://doi.org/10.3389/fvets.2019.00233

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Abstract

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.

Highlights

Host defense peptides (HDPs) are important effector molecules of the immune system with both antimicrobial and immunomodulatory properties [1,2,3,4,5]
Human LL37 was purchased from QCB (Hopkinton, MA, USA), synthetic peptide innate defense regulator (IDR)-1002 was obtained from Dr Robert Hancock (University of British Columbia, Canada), porcine PR39 was synthetized in house by Dr Sam Attah-Poku, and poly(I:C) was purchased from Sigma-Aldrich (St-Louis, MO, USA) and used at 10 μg/mL
To assess whether the ability of selected peptides to inhibit porcine respiratory and reproductive syndrome virus (PRRSV) replication was due to modified cell signaling or direct interaction with poly(I:C), a gel migration analysis of poly(I:C)HDP complexes was carried out to identify potential interactions between the peptides and poly(I:C)

Summary

Introduction

Host defense peptides (HDPs) are important effector molecules of the immune system with both antimicrobial and immunomodulatory properties [1,2,3,4,5]. LL37 and the proline-arginine-rich peptide PR39 are both members of the cathelicidin family with LL37 representing the C-terminal part of the human cationic antimicrobial protein (hCAP) 18 and PR39 being a full-length porcine cathelicidin [2, 4]. These two HDPs are expressed by the intestinal and the respiratory mucosa and are produced by epithelial cells, macrophages, and neutrophils [2, 4, 6]. Like LL37, this HDP is involved in the antimicrobial response, has immunomodulatory properties, and several other biological functions [2, 6, 23]

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