Oral Presentation International Veterinary Immunology Symposium 2016

Interleukin-1 receptor antagonist (IL-1Ra): a potential negative immunomodulatory mediator during an early phase of Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection (#41)

Teerawut Nedumpun 1 , Patcharee Ritprajuk 2 , Tanapat Palaga 3 , Sanipa Suradhat 4 5
  1. Interdisciplinary Program of Medical Microbiology, Chulalongkorn University , Bangkok
  2. Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
  3. Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
  4. Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
  5. Center of Excellent for Emerging and Re-emerging Infectious Disease in Animals (CU-EIDAs), Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a swine viral pathogen, which has been reported to possess several immunomodulatory properties. During an early phase of PRRSV infection, weak and delayed induction of pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and antiviral cytokines (type 1 IFN) production was observed. Currently, the immunosuppressive mechanism(s) of PRRSV during an early phase of infection remains incompletely understood. Our preliminary microarray analysis demonstrated that PRRSV infected monocyte derived dendritic cells (MoDCs) significantly upregulated interleukin-1 receptor antagonist (IL-1Ra) gene expression. IL-1Ra is known as early anti-inflammatory cytokine. IL-1Ra controls inflammatory responses by competitive binding to interleukin-1 receptor (IL-1R), which subsequently prohibits an intracellular IL-1 signaling cascade. Here, we aimed to investigate the effect of PRRSV on IL-1Ra production. In an in vitro model, porcine PBMCs were cultured with 0.1 m.o.i. of PRRSV or mock-infected MARC-145 cell lysate for 48 hours. The presence of PRRSV significantly increased IL-1Ra producing cell in the culture. Myeloid subpopulation was found to be the major IL-1Ra producer in the system. In an in vivo model, PRRSV-free crossbred pigs were vaccinated with PRRSV modified lived vaccine (MLV) US strain or PBS. Subsequently, PBMCs were collected and subjected to immunnofluorescent staining. Consistent to the in vitro findings, PRRSV infection significantly enhanced numbers of IL-1Ra producing cells in the myeloid subpopulation on 4 and 7 days post-inoculation. It has been previously shown that IL-1Ra can suppress the production of IL-1 and TNF-α in macrophages. Thus, IL-1Ra could be a potential negative immunomodulatory factor, which plays a role in suppression of innate cytokine production during the early phase of PRRSV infection. The implication of PRRSV-induced IL-1Ra production on the immune system is currently under investigated. Our finding could provide better understanding in the immunopathogenesis of PRRSV.