Negative Immunomodulatory Effects of Type 2 Porcine Reproductive and Respiratory Syndrome Virus-Induced Interleukin-1 Receptor Antagonist on Porcine Innate and Adaptive Immune Functions

Abstract

Impaired innate and adaptive immune responses are evidenced throughout the course of PRRSV infection. We previously reported that interleukin-1 receptor antagonist (IL-1Ra) was involved in PRRSV-induced immunosuppression during an early phase of infection. However, the exact mechanism associated with PRRSV-induced IL-1Ra immunomodulation remains unknown. To explore the immunomodulatory properties of PRRSV-induced IL-1Ra on porcine immune functions, monocyte-derived dendritic cells (MoDC) and leukocytes were cultured with type 2 PRRSV, and the immunological role of IL-1Ra was assessed by addition of anti-porcine IL-1Ra Ab. The results demonstrated that PRRSV - induced IL-1Ra reduced phagocytosis, surface expression of MHC II (SLA-DR) and CD86, as well as downregulation of IFNA and IL1 gene expression in the MoDC culture system. Interestingly, IL-1Ra secreted by the PRRSV-infected MoDC also inhibited T lymphocyte differentiation and proliferation, but not IFN-γ production. Although PRRSV-induced IL-1Ra was not directly linked to IL-10 production, it contributed to the differentiation of regulatory T lymphocytes (Treg) within the culture system. Taken together, our results demonstrated that PRRSV-induced IL-1Ra downregulates innate immune functions, T lymphocyte differentiation and proliferation, and influences collectively with IL-10 in the Treg induction. The immunomodulatory roles of IL-1Ra elucidated in this study increase our understanding of the immunobiology of PRRSV.

The influence of source of porcine colostrum in development of early immune ontogeny in the piglet

“…In contrast, piglets fed milk replacer are associated with signi cantly increased concentrations for IL-1ra and IL-8. IL-1 receptor antagonist (IL-1ra) is an anti-in ammatory agent that reduces in ammation by blocking the binding of the agonist receptor ligands 54 . Probably, some properties of the milk replacer composition may be antigenic and supplementary analysis may be useful to detect the degree of immune reactivity against antigens of these products.…”

The T-Cell Response to Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)

“…The balance between these two important CD4 + T-cell subsets is crucial for an effective and healthy immune response. The two research groups reported that PRRSV-2 stimulates Tregs [8,10,11,12,46]. Based on those reports, it has been speculated that the PRRSV-2 is shifting that balance of the CD4 T-cell response towards Tregs.…”

“…One main characteristic of PRRSV-2 is its ability to actively suppress the host immune response facilitating prolonged viremia, persistence in tissues, and the development of chronic secondary infections associated with PRDC. The following mechanisms of PRRSV-2 immune suppression were reported: The inhibition of NK cell activity and Type I Interferons production in the innate response [3]; the induction of PRRSV-2 specific CD4 + CD25 + regulatory T cells (Tregs) [4,5,6,7,8,9,10,11,12]; and the dysregulation of T-cell development in the neonatal thymus [13]. Ideally for the host, an effective T-cell response to PRRSV-2 would display the characteristics of a strong T-helper type 1 (Th1) response: Early CD4 + Th proliferation and significant production of IFN-γ; the differentiation of PRRSV-reactive Th cells into both, lymph node homing central memory (T CM ) and tissue homing effector memory (T EM ) populations [14]; and the induction of multifunctional memory T cells (T multi ).…”

Swine Dendritic Cell Response to Porcine Reproductive and Respiratory Syndrome Virus: An Update

“…In addition to the induction of Tregs, Nedumpun et al. showed that PRRSV-infected moDCs induced the expression and production of IL-1Ra, which is a natural suppressor of the inflammatory response ( 59 , 60 ). Chen et al.…”

“…In addition to the induction of Tregs, Nedumpun et al showed that PRRSV-infected moDCs induced the expression and production of IL-1Ra, which is a natural suppressor of the inflammatory response (59,60). Chen et al ( 61) demonstrated that the viral N protein and nsp10 enhanced the production of CD83, an inhibitor of DC-mediated T-cell proliferation (62), via activation of NF-KB and Sp1 signaling pathways (61).…”