轮状病毒SA11持续胃肠道感染对IL-10基因敲除小鼠肠道炎症的抑制作用OA

Objective:To investigate the dynamic regulatory effects of persistent infection with rotavirus(RV)strain SA11 on intestinal inflammation in interleukin-10(IL-10)gene-deficient(IL-10-/-)mice,and to elucidate its underlying mechanism.Methods:The monkey embryonic kidney MA104 cells were routinely cultured.The indirect immunofluorescence assay was used to detect the viral titer of SA11 in MA104 cells.A total of 20 SPF wild-type C57BL/6(WT-B6)mice were selected as control group,while twenty IL-10 gene knockout C57BL/6 mice(IL-10-/--B6)were assigned to experimental group.A persistent infection model was established by daily oral gavage with 1×106 FFU·mL-1 SA11 suspension for 42 consecutive days.Both fecal and intestinal tissue samples were collected from the mice in two groups weekly.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the copy numbers of the RV capsid protein VP6 gene in feces and the expression levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and transforming growth factor-β(TGF-β)mRNA in colorectal tissues of the mice in two groups.HE staining was used to observe the histopathological morphology of duodenal and jejunal tissues of the mice in two groups.Results:The indirect immunofluorescence assay determined the titer of the SA11 virus to be 1×106 FFU·mL-1.During the first 21 days of persistent RV infection,the VP6 gene copy numbers in the feces of the mice in both IL-10-/--B6 and WT-B6 groups remained at low levels,with no statistically significant difference between two groups(P>0.05).After 28 d of persistent infection,compared with WT-B6 group,the copy number of VP6 gene in the feces of the mice in IL-10-/--B6 group was significantly increased(P<0.05).Compared with the status before infection,the expression levels of IL-1β and TGF-α mRNA in the colorectal tissues of the mice in WT-B6 group after RV infection were significantly increased(P<0.001),the expression levels of IL-1β and TGF-α mRNA in IL-10-/--B6 group were significantly decreased(P<0.001),and the expression levels of TGF-β mRNA in both groups were significantly increased(P<0.001).Conclusion:Persistent gastrointestinal infection with RV strain SA11 may alter the intestinal immune microenvironment in the IL-10-/-mice,manifested by downregulated expression of IL-1β and TNF-α and upregulated expression of TGF-β in colorectal tissue,thereby alleviating intestinal inflammation.This regulatory network suggests that RV may influence the progression of intestinal inflammation by reshaping the intestinal immune balance.