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Induction of interleukin-1 receptor antagonist (IL-1Ra) by porcine reproductive and respiratory syndrome virus (PRRSV) |
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| รหัสดีโอไอ | |
| Title | Induction of interleukin-1 receptor antagonist (IL-1Ra) by porcine reproductive and respiratory syndrome virus (PRRSV) |
| Creator | Teerawut Nedumpun |
| Contributor | Sanipa Suradhat, Tanapat Palaga, Patcharee Ritprajak |
| Publisher | Chulalongkorn University |
| Publication Year | 2560 |
| Keyword | Porcine reproductive and respiratory syndrome, Dendritic cells, Interleukin-1, โรคพีอาร์อาร์เอส, เซลล์ใยประสาทนำเข้า, อินเตอร์ลิวคิน-1 |
| Abstract | Porcine respiratory and reproductive syndrome virus (PRRSV) is one of the major pathogens affecting pig production industry worldwide. Impaired innate and adaptive immune responses are evidenced through the course of PRRSV infection. Several evidences indicate that PRRSV suppresses host immune responses via several immune evasion strategies. Interleukin-1 receptor antagonist (IL-1Ra) is known as an early inhibitory cytokine that suppresses innate immune functions and T lymphocyte responses. The aims of this study were to explore the induction of IL-1Ra by PRRSV and the negative immunomodulatory effects of PRRSV-induced IL-1Ra on porcine immune responses.In this study, the previous monocytes-derived dendritic cells (MoDC) generation protocol was modified, based on the human and mouse primary DC culture system. The modified protocol required fewer monocytes, but generated higher numbers of CD1+ MoDC. The MoDC from the modified protocol also exhibited increased antigen uptake and IFN- production. Therefore, the modified protocol is expedient and reliable for generating potent MoDC. The induction of IL-1Ra by PRRSV was determined both in vitro and in vivo. Type 2 PRRSV increased both IL1RA gene expression and IL-1Ra protein production in the cultured porcine leukocytes. The enhanced production of IL-1Ra was further confirmed in the pigs immunized with a modified-live PRRSV vaccine. Myeloid cell population appeared to be the major IL-1Ra producer in the system. In contrast to the type 2 PRRSV, the highly pathogenic (HP) PRRSV did not induce IL1RA gene expression. The immunomodulatory roles of type 2 PRRSV-induced IL-1Ra on porcine immune responses were further explored using an in vitro IL-1Ra neutralization assay. The findings demonstrated that PRRSV-induced IL-1Ra was responsible for inhibition of phagocytosis, expressions of MHC II (SLA-DR) and CD86 molecules, as well as down regulation of IFNA and IL1 gene expression. Furthermore, IL-1Ra obtained from PRRSV-infected MoDC also interfered with effector T lymphocyte differentiation and proliferation. Interestingly, although PRRSV-induced IL-1Ra was not directly linked to the IL-10 production, it contributed to the differentiation of porcine regulatory T lymphocytes (Treg).Our findings demonstrated that PRRSV could enhance IL-1Ra production in infected pigs. Moreover, PRRSV-induced IL-1Ra possessed negative immunomodulatory effects on porcine innate immune functions and T lymphocyte responses. The elucidated roles of IL-1Ra from this study help completing the understanding in mechanism of PRRSV immunopathogenesis and may eventually lead to better disease intervention |
| URL Website | cuir.car.chula.ac.th |
