Autor: |
Franzoni G; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy., Zinellu S; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy., Razzuoli E; National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 16129 Genova, Italy., Mura L; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy.; Department of Biomedical Sciences, School of Medicine, University of Sassari, 07100 Sassari, Italy., De Ciucis CG; National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 16129 Genova, Italy., De Paolis L; National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 16129 Genova, Italy., Carta T; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy.; Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy., Anfossi AG; Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy.; Mediterranean Center for Disease Control (MCDC), University of Sassari, 07100 Sassari, Italy., Graham SP; The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK., Chessa B; Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy., Dei Giudici S; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy., Oggiano A; Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy. |
Abstrakt: |
Toll-like receptor 2 (TLR2) ligands are attracting attention as prophylactic and immunopotentiator agents against pathogens, including viruses. We previously reported that a synthetic diacylated lipopeptide (Mag-Pam2Cys_P48) polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. Here, we investigated its role in modulating monocyte-derived macrophage (moMΦ) responses against African swine fever virus (ASFV), the etiological agent of one of the greatest threats to the global pig industry. Two ASFV isolates were compared: the attenuated NH/P68 and the virulent 26544/OG10. No effect on virus infection nor the modulation of surface markers' expression (MHC I, MHC II DR, CD14, CD16, and CD163) were observed when Mag-Pam2Cys_P48 treated moMΦ were infected using a multiplicity of infection (MOI) of 1. Mag-Pam2Cys_P48 treated moMΦ released higher levels of IL-1α, IL-1β, IL-1Ra, and IL-18 in response to infection with NH/P68 ASFV compared to 26544/OG10-infected and mock-infected controls. Surprisingly, when infected using a MOI of 0.01, the virulent ASFV 26544/OG10 isolate replicated even slightly more efficiently in Mag-Pam2Cys_P48 treated moMΦ. These effects also extended to the treatment of moMΦ with two other lipopeptides: Mag-Pam2Cys_P80 and Mag-Pam2Cys_Mag1000. Our data suggested limited applicability of TLR2 agonists as prophylactic or immunopotentiator agents against virulent ASFV but highlighted the ability of the virulent 26544/OG10 to impair macrophage defenses. |