Study On The Lateralization Of Mice Cerebral Cortex Immune Function Under Physiological And Influenza Infection Conditions

Background: Certain body functions executed by two hemispheres of the brain,that means there is asymmetry and specialization,which is called brain lateralization.The brain immune function also has the partial localization phenomenon.For example,the regulation of astrocytes and the microglia in brain immune micro-environment and immune response in pathogenesis has the partial localization phenomenon.In cerebral cortex injury,the response of immune cells such as,macrophages,T cells and B cells on the left and right sides may also be biased.Influenza virus infection can trigger the immune response of the central nervous system,which can lead to acute encephalopathy of influenza in severe cases.However,it is still unclear to state that which side of cerebral cortex plays role to initiate immune response in physiological conditions and during influenza virus infection.This study was designed to investigate the differences of the immune response initiated by either side of cerebral cortex during physiological condition or prodromal and acute phases of influenza A virus H1N1 infection.Methods: RNA-seq and analysis was performed on the left and right cerebral cortex of BALB/c mice under physiological and influenza infection conditions.Differential genes and inflammatory factors related to immune function of left and right cerebral cortex under different conditions were analyzed and verified by RT-qPCR and ELISA.Results: 1.Under physiological conditions,the expression levels of Itga2 and Igkc in the left cerebral cortex of mice were higher than those in the right cerebral cortex,and the expression levels of Il5,Defb1,Ifitm7,Bik and Il1 rn in the right cerebral cortex were higher than those in the left cerebral cortex.2.In the prodromal phase of H1N1 infection,the expression level of S100a7 a in the left cerebral cortex of the control group was higher than that in the right cerebral cortex,and the expression levels of Ngb,Baiap3,Nxph4,Igsf1,Cd36,Lefty2 and S100a3 in the right cerebral cortex were higher than those in the left cerebral cortex.The expression levels of Baiap3,Cd36,Ntf3,Ngb,Lefty2,Ccl7,Tnfrsf17,Igbp1 b and Ccl27 a in the left cerebral cortex of infected mice were higher than those in the right cerebral cortex,and the expression levels of Sapcd1,Ntf5 and Ltb4r2 in the right cerebral cortex were higher than those in the left cerebral cortex.3.In the acute phase of H1N1 infection,the expression levels of Cxcr4,Baiap2l1,Tiaf2,Tnfrsf4,Itga4,Ifi208 and Ccr10 in the left cerebral cortex of the control group were higher than those in the right cerebral cortex,and the expression levels of Il20 ra,Cd4,Ighg1,Igha,Jchain,Igkc,Gdnf,Slpi,Ifi202 b,Pilra,Ntrk1,S100a3,Tgtp2 and Il21 in the right cerebral cortex were higher than those in the left cerebral cortex.The expression levels of Baiap3,Ildr1,Ngfr,Cd36,Igsf1,Nxph4,Cd209 c,Igbp1b,Lefty2,Ccl27 a,Traf1,Itgb1bp2,Cxcl11 in the left cerebral cortex of infected mice were higher than those in the right cerebral cortex,and the expression levels of Cd52 and Cd300 e in the right cerebral cortex were higher than those in the left cerebral cortex.4.In the prodromal and acute stages of H1N1 infection,the number of immune related genes expressed in the infected group were higher than the control group.The prodromal stage mainly included the genes for the regulation of signaling receptor activity,receptor ligand activity,and cytokine receptor binding.The acute stage mainly included the genes for the regulation of signaling receptor activity,positive regulation of secretion,positive regulation of secretion by cell,and receptor regulator activity.The expression levels of differentially expressed genes enriched in related functions in the left cerebral cortex were higher than those in the right cerebral cortex.5.In the prodromal and acute stages of H1N1 infection,the differentially expressed genes was high in the right cerebral cortex of the control group were mainly responsible for neuroactive ligand-receptor interaction related pathways,while the same genes were highly induced by left cerebral cortex during influenza virus infection.6.RT-qPCR results showed that BDNF,CCR5,IL-1β,MIF,TLR3 and other immune related molecules had intra-group or inter-group differences in the left and right cerebral cortex of the control group or the infection group.7.ELISA results showed that immune related cytokines such as IL-1α,IL-2,IL-10,IL-12,KC(CXCL1)and MIP-2(CXCL2)at different stages of influenza infection had intra-group or inter-group differences in the left and right cerebral cortex of the control group or the infection group.Conclusion: There are some differences in the expression of genes related to immune function in the left and right cerebral cortex under physiological conditions,and the expression of genes related to immune function in the right cerebral cortex is more prominent.The differences in gene expression between left and right cerebral cortex were more significant under influenza infection,and the gene expression related to immune function in left cerebral cortex was more prominent.The immune related genes in the cerebral cortex have certain left and right lateralization at the transcription and protein levels.