Study On The Expression Of IL-4 And Related Immune Response In Pigs Induced By PRRSV Reinfection

Porcine Reproductive and Respiratory Syndrome?PRRS?is an acute infectious disease of harming the global pig industry which is caused by Porcine Reproductive and Respiratory Syndrome Virus?PRRSV?.The disease mainly causes reproductive disorders of sows,respiratory disease,immunosuppression and persistent infections of fattening pigs and piglets in clinical.Compared with classical PRRSV,the molecular feature of HP-PRRSV is that a total of 30 amino acids at positions 482 and 533-561 of the Nsp2 gene are deleted.As we all know,there are differences in the pathogenicity of different virulence PRRSV strains.Some research results have shown that strains of different virulence can have a very subtle effect,even more disperse replication or induce apoptosis phenomenon in addition to the infection of alveolar macrophages.Moreover,HP-PRRSV has higher cell phagocytic properties than classic strains,especially causing damage to peripheral immune organs.The Th1-Th2 immune response model provides a systematic research framework for the immune response of the body after being infected by infectious pathogens.Interleukin-4?IL-4?is a high-efficiency cytokine secreted by activated T lymphocytes,basophils and mast cells,which plays an important role in this immune response model.IL-4 plays a major role in T cell development and is thought to promote the differentiation of T helper cells into Th2 cells during the immune response,and IL-4 can also enhance antigen-specific humoral immunity response.A large number of studies have shown that PRRSV primary infection cannot induce the production of IL-4,but Wang Gang and Yu Ying showed the cytokine storms of IL-4appeared in the peripheral blood of piglets during re-infection of HP-PRRSV HuN4.So,what are the laws of IL-4 induced by PRRSV of different virulence infection and reinfection,and what role does it play in the body,and what is the relationship between IL-4 and cellular immunity and humoral immunity.However,there are few reports on relevant literature at prerent,and we cannot draw a clear conclusion.In this study,we will explore the scientific issues we raised above.The experiment randomly divided 30 26-day-old double-negative piglets with PRRSV antigen and antibody into 4 groups.Group 2?n=7?,Group 3?n=7?,Group 4?n=7?were all given the first nasal inoculation with HP-PRRSV JXA1 attenuated strain(1×10⁵ TCID₅₀/head)at the age of 30days.After 28 days,they were inoculated with PBS,HP-PRRSV JXA1 attenuated strain(1×10⁵TCID₅₀/head)and HP-PRRSV JXA1 virulent strain?1×10⁵TCID50/head?respectively.Group 1?n=9?were vaccinated twice PBS.This study use the peripheral immune organs?lymph nodes and spleen?as a model to carry out preliminary studies on the dynamic changes of IL-4,T lymphocytes,B lymphocytes and PRRSV viral load.Meanwhile,the cytokine levels?IL-4,IFN-??,lymphocyte ratio changes?CD3⁺,CD3⁺CD4⁺,CD3⁺CD8⁺,CD4⁺CD8⁺T lymphocyte changes,lymphocyte transformation rate?,antibody levels?anti-N protein antibody level,neutralizing antibody level?and viral load in peripheral blood of piglets are tested periodically?0 d,7 d,14 d,21 d,28 d,35 d,42 d,49 d?.The results of this study showed that reinfection with both attenuated and virulent strains of HP-PRRSV JAX1 induced a dramatic increase of IL-4 in peripheral blood of piglets and higher mRNA and protein levels of IL-4 in the peripheral immune organs?lymph nodes and spleen?;At the same time,we found that the migration of IL-4 occurred after HP-PRRSV reinfection.Its location was mainly concentrated around the lymph nodules of the lymph nodes,paracortical regions,the marginal area of the spleen and the periarterial lymphatic sheath region after the primary infection.After reinfection,it mainly gathers in the lymph nodules of lymph nodes and spleen and scattered in the red pulp of the spleen.Lymph nodules of lymph nodes and the spleen,the red pulp of the spleen are known to be the main areas of B cell aggregation,so a large amount of IL-4 accumulates in lymph nodules and the red pulp of the spleen leads us to speculate that the biological function of SwIL-4 may be similar to the biological function of the mice or humans after reinfection of HP-PRRSV,that is,SwIL-4 can interact with B cells,and even it can promote the proliferation and differentiation of B cells and the production of antibody levels.Through the study of peripheral blood,the results show that:compared with the same period of the primary infection,the level of anti-N protein antibody,neutralizing antibody and CD3⁺CD8⁺T lymphocyte of the peripheral blood showed an upward trend but the CD3⁺CD4⁺T lymphocyte showed a downward trend and the virus cycle was shorter than primary infection after HP-PRRSV JXA1 reinfected.As for the effects of IL-4 on the humoral immunity and cellular immunity of piglets infected with HP-PRRSV is still needed further research.