AUTHOR=Chen Xiaolan , Wang Zhijun , Chen Yangfeng , Akinci Ibrahim , Luo Wei , Xu Yibin , Jebessa Endashaw , Blake Damer , Sparks Nick , Hanotte Olivier , Nie Qinghua 

TITLE=Transcriptome analysis of differentially expressed circRNAs miRNAs and mRNAs during the challenge of coccidiosis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.910860

DOI=10.3389/fimmu.2022.910860

ISSN=1664-3224

ABSTRACT=<p>Avian coccidiosis is a common enzootic disease caused by infection of <italic>Eimeria</italic> species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to <italic>Eimeria</italic> species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during <italic>Eimeria</italic> species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from <italic>Eimeria tenella</italic>-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (<italic>DEcircRNAs</italic>), 31 differentially expressed miRNAs (<italic>DEmiRNAs</italic>), and 820 differentially expressed genes (<italic>DEmRNAs</italic>) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and <italic>Eimeria</italic> spp. Functional validation of a significantly differentially expressed circRNA, <italic>circMGAT5</italic>, revealed that <italic>circMGAT5</italic> could sponge <italic>miR-132c-5p</italic> to promote the expression of the <italic>miR-132c-5p</italic> target gene <italic>monocyte to macrophage differentiation-associated</italic> (<italic>MMD</italic>) during the infection of <italic>E. tenella</italic> sporozoites or LPS stimulation. Pathologically, knockdown of <italic>circMGAT5</italic> significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, <italic>F4/80</italic> and <italic>MHC-II</italic>, which indicated that <italic>circMGAT5</italic> might inhibit the activation of macrophage. <italic>miR-132c-5p</italic> markedly facilitated the expression of <italic>F4/80</italic> and <italic>MHC-II</italic> while <italic>circMGAT5</italic> could attenuate the increase of <italic>F4/80</italic> and <italic>MHC-II</italic> induced by <italic>miR-132c-5p</italic>, indicating that <italic>circMGAT5</italic> exhibited function through the <italic>circMGAT5</italic>-<italic>miR-132c-5p</italic>-<italic>MMD</italic> axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during <italic>E. tenella</italic> infection. Among these, <italic>circMGAT5</italic> may inhibit the activation of macrophages through the <italic>circMGAT5</italic>-<italic>miR-132c-5p</italic>-<italic>MMD</italic> axis to participate in the immune response induced by <italic>Eimeria</italic> infection.</p>