TY - JOUR

T1 - Dynamic miRNA profile of host T cells during early hepatic stages of Schistosoma japonicum infection

AU - Giri, Bikash R.

AU - Li, Shun

AU - Fang, Chuantao

AU - Qiu, Lin

AU - Yan, Shi

AU - Pakharukova, Maria Y.

AU - Cheng, Guofeng

N1 - Funding Information: This study was supported, in whole or in part, by the Key Program for International S&T Cooperation Projects of China (2021YFE0191600 to GC), the State Key Laboratory of Veterinary Etiological Biology (SKLVEB2020KFKT018 to GC), the Research Fund for International Young Scientists from NNSF (31950410564 to BG) and the National Natural Science Foundation of China (31472187 and 31672550 to GC). The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation. Publisher Copyright: Copyright © 2022 Giri, Li, Fang, Qiu, Yan, Pakharukova and Cheng.

PY - 2022/9/2

Y1 - 2022/9/2

N2 - Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4+ T cells play critical roles in response to Schistosoma infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with Schistosoma infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of S. japonicum infected C57BL/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL/6J mice blood showed that miR-486b-5p/3p expression was significantly downregulated and linked to various T cell immune responses and miR-375-5p was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, etc. Whereas hepatic T cells showed miR-466b-3p, miR-486b-3p, miR-1969, and miR-375 were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and in vitro cultured EL-4 cells treated with S. japonicum worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of Ctla4, Atg5, Hgf, Vcl and Arpc4 and a decreased expression of Fermt3, Pik3r1, Myd88, Nfkbie, Ppp1r12a, Ppp3r1, Nfyb, Atg12, Ube2n, Tyrobp, Cxcr4 and Tollip. Overall, these results unveil the comprehensive repertoire of T cell miRNAs during S. japonicum infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of S. japonicum infection.

AB - Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4+ T cells play critical roles in response to Schistosoma infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with Schistosoma infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of S. japonicum infected C57BL/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL/6J mice blood showed that miR-486b-5p/3p expression was significantly downregulated and linked to various T cell immune responses and miR-375-5p was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, etc. Whereas hepatic T cells showed miR-466b-3p, miR-486b-3p, miR-1969, and miR-375 were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and in vitro cultured EL-4 cells treated with S. japonicum worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of Ctla4, Atg5, Hgf, Vcl and Arpc4 and a decreased expression of Fermt3, Pik3r1, Myd88, Nfkbie, Ppp1r12a, Ppp3r1, Nfyb, Atg12, Ube2n, Tyrobp, Cxcr4 and Tollip. Overall, these results unveil the comprehensive repertoire of T cell miRNAs during S. japonicum infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of S. japonicum infection.

KW - immune response

KW - infection

KW - microRNA

KW - Schistosoma japonicum

KW - T cell

KW - MicroRNAs/genetics

KW - Schistosomiasis japonica/genetics

KW - Mice, Inbred C57BL

KW - CTLA-4 Antigen/metabolism

KW - Myeloid Differentiation Factor 88/metabolism

KW - Animals

KW - Liver/metabolism

KW - T-Lymphocytes/metabolism

KW - Mice

KW - Intracellular Signaling Peptides and Proteins/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85138140408&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2022.911139

DO - 10.3389/fimmu.2022.911139

M3 - Article

C2 - 36119054

AN - SCOPUS:85138140408

VL - 13

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 911139

ER -