PMID- 34579246 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211001 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 9 IP - 9 DP - 2021 Sep 10 TI - Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) Promotes M1 Repolarization of Porcine Alveolar Macrophages and Th1 Type Response. LID - 10.3390/vaccines9091009 [doi] LID - 1009 AB - The polarization status of porcine alveolar macrophages (PAMs) determines the infectivity of porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV infection skews macrophage polarization toward an M2 phenotype, followed by T-cells inactivation. CD163, one of the scavenger receptors of M2 macrophages, has been described as a putative receptor for PRRSV. In this study, we examined two types of PRRSV-2-derived recombinant antigens, A1 (g6Ld10T) and A2 (lipo-M5Nt), for their ability to mediate PAM polarization and T helper (Th1) response. A1 and A2 were composed of different combination of ORF5, ORF6, and ORF7 in full or partial length. To enhance the adaptive immunity, they were conjugated with T cells epitopes or lipidated elements, respectively. Our results showed that CD163(+) expression on PAMs significantly decreased after being challenged with A1 but not A2, followed by a significant increase in pro-inflammatory genes (TNF-alpha, IL-6, and IL-12). In addition, next generation sequencing (NGS) data show an increase in T-cell receptor signaling in PAMs challenged with A1. Using a co-culture system, PAMs challenged with A1 can induce Th1 activation by boosting IFN-gamma and IL-12 secretion and TNF-alpha expression. In terms of innate and T-cell-mediated immunity, we conclude that A1 is regarded as a potential vaccine for immunization against PRRSV infection due to its ability to reverse the polarization status of PAMs toward pro-inflammatory phenotypes, which in turn reduces CD163 expression for viral entry and increases immunomodulation for Th1-type response. FAU - Wahyuningtyas, Rika AU - Wahyuningtyas R AUID- ORCID: 0000-0002-4150-266X AD - Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. FAU - Lai, Yin-Siew AU - Lai YS AUID- ORCID: 0000-0003-2963-9038 AD - Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. FAU - Wu, Mei-Li AU - Wu ML AD - Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Department of Food Science, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. FAU - Chen, Hsin-Wei AU - Chen HW AUID- ORCID: 0000-0002-3207-2397 AD - National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan. AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung 400, Taiwan. AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 800, Taiwan. FAU - Chung, Wen-Bin AU - Chung WB AD - Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. FAU - Chaung, Hso-Chi AU - Chaung HC AD - Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Department of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Flow Cytometry Center, Precision Instruments Center, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. FAU - Chang, Ko-Tung AU - Chang KT AUID- ORCID: 0000-0001-9383-831X AD - Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Flow Cytometry Center, Precision Instruments Center, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. AD - Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan. LA - eng GR - MOST 107-3017-F-020-001-, MOST 108-3017-F-020 -001-, MOST 109-2634-F-020-001-, MOST 110-2634-F-020-001-, MOST 109-2314-B-020-002/Ministry of Science and Technology, Taiwan/ PT - Journal Article DEP - 20210910 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC8473084 OTO - NOTNLM OT - CD163 OT - M1 OT - M2 OT - PAMs OT - PRRSV OT - Th1 COIS- The authors declare no conflict of interest. EDAT- 2021/09/29 06:00 MHDA- 2021/09/29 06:01 PMCR- 2021/09/10 CRDT- 2021/09/28 01:29 PHST- 2021/06/22 00:00 [received] PHST- 2021/09/06 00:00 [revised] PHST- 2021/09/07 00:00 [accepted] PHST- 2021/09/28 01:29 [entrez] PHST- 2021/09/29 06:00 [pubmed] PHST- 2021/09/29 06:01 [medline] PHST- 2021/09/10 00:00 [pmc-release] AID - vaccines9091009 [pii] AID - vaccines-09-01009 [pii] AID - 10.3390/vaccines9091009 [doi] PST - epublish SO - Vaccines (Basel). 2021 Sep 10;9(9):1009. doi: 10.3390/vaccines9091009.