Journal
VACCINES
Volume 9, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/vaccines9070692
Keywords
pig; macrophages; TLR2 agonist; cytokines; surface markers; IFN-alpha subtypes; toll-like receptors; IL-10
Categories
Funding
- Italian Ministry of Health [IZSUM PSRC 1/2018, IZS PLV 08/19 RC]
- UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant [BBS/E/I/00007031]
- BBSRC [BBS/E/I/00007031] Funding Source: UKRI
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Mag-Pam2Cys can polarize porcine macrophages towards a proinflammatory antimicrobial phenotype, enhancing activation markers and phagocytotic activity, while also regulating the expression of various factors and cellular responses to avoid potentially harmful consequences.
Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moM Phi). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moM Phi. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-alpha subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-alpha 3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.
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