The CXCL10/CXCR3 signaling pathway and IL-15 play indispensable functions in recruiting and activating HSV-1 specific CD8+?T cells in trigeminal ganglia with HSV-1 latency infection [29, 30]

The CXCL10/CXCR3 signaling pathway and IL-15 play indispensable functions in recruiting and activating HSV-1 specific CD8+?T cells in trigeminal ganglia with HSV-1 latency infection [29, 30]. from representative RE, TLE and TBI brain samples was analyzed using an In Situ Cell Death Detection Kit, and visualized by fluorescence method. Bar: 50?m. Fig. S6. The cytokine levels in RE and TLE cerebrospinal fluid (CSF). CSF from RE and TLE patients were analyzed using Aimplex Human Multiplex Immunoassays packages according to the manufacturers training. The cytokine levels were expressed as mean??std and analyzed with a two-tailed Student Implitapide ttest (n?=?9 for RE and n?=?8for TLE). *: p? ?0.05. Table S1. List of antibodies. 12974_2022_2379_MOESM1_ESM.pdf (803K) GUID:?AB6E6612-3B82-42E7-A6CF-2BFC324BBE47 Data Availability StatementData supporting the conclusions of this article are presented in this manuscript. Abstract Background The etiology of Rasmussen’s encephalitis (RE), a rare chronic neurological disorder characterized by CD8+?T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is usually unclear. Methods HHVs contamination and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+?T Implitapide cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex circulation cytometry. Cell apoptosis was visualized by TUNEL staining. Viral contamination, immune Implitapide response and the severity of unihemispheric atrophy were subjected to correlation analysis. Results Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+?T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon- level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. Conclusions Compared with TBI, both RE and TLE experienced prevalently HHV contamination and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV contamination, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-022-02379-0. were detected (Fig.?1A and B). In TBI which represented brains from healthy people, the HHV-positive rate varied from 0 to 30%, and 40% experienced no antigen detected, indicating that HHV antigens positive rate in brains were not as common as the high seropositive rate in the population. In contrast, antigens of the four HHVs were universally detected in RE and TLE brains with different positive rates, which in both were significantly higher than those Implitapide in TBI. Coinfection by more than one HHV were Implitapide very common in RE and TLE samples. On average, each of them experienced 3 types of HHVs coinfected. In 18% of RE cases and 2% of TLE cases, all four HHV antigens were simultaneously detected (Additional file 1: Fig. S1A). Open in a separate window Fig. 1 The detection of HHVs in RE and TLE brain samples and its correlation with MRI severity. A Sections from 30 RE, 20 TLE and 16 TBI brain samples was analyzed using immunohistochemistry (IHC) with antibodies against numerous HHVs and B were scored according to criteria explained in the Material and Methods and analyzed using a two-tailed MannCWhitney U test (*: em p /em ? ?0.05; **: em p /em ? ?0.01, ns: nonsignificance). Bar: 100?m. C A representative magnetic resonance imaging (MRI) scan of an RE patient. The MRI scan shows a grey or white matter T2/FLAIR hyperintense signal and a hyperintense signal or atrophy of the cortex (arrowhead) and ipsilateral caudate head (arrow). The severity of RE was determined by grading brain atrophy detected by MRI and was expressed as an MRI score. The scoring plan for the MRI was as Adcy4 following: 0 means no atrophy and no ventricle or sulcus enlargement, 1 means poor atrophy with the sulci deepening.