Comparative transcriptome analysis of normal and CD44-deleted mouse brain under chronic infection with Toxoplasma gondii

Abstract

Toxoplasma gondii is a globally-distributed intracellular parasitic protozoon with wide host range. Chronic infection is the most prevalent form of T. gondii infection, which can lead to significant damage. CD44 plays an important role in body's immune response, however, little is known about the function and mechanism of CD44 in T. gondii infection until now. In the present study, total RNA isolated from four groups including C57BL/6 mouse (C57), C57BL/6△CD44 mouse(C57△CD44), C57BL/6 mouse infected with T. gondii (C57-TG) and C57BL/6△CD44 infected with T. gondii (C57△CD44-TG)were subjected to comparative transcriptome analyses using RNA-seq techniques to explore the possible function of CD44 in mouse brain during chronic Toxoplasma infection. The results indicated a total of 35,908, 54,428, 51,473 and 22,387 unigenes were annotated in KOG, Swissprot, GO and KEGG databases by transcriptome analysis, respectively, and all the databases shared 9,833 unigenes. Subsequently, differentially expressed GO terms and enriched KEGG Pathways showed 20,303 unigenes were annotated belonging to three main GO categories (namely biological process, cellular component and molecular function) and six main KEGG categories (cellular processes, environmental information processing, genetic information processing, human diseases, metabolism and organismal systems) between normal C57 and C57△CD44 mice, as well as for C57-TG and C57△CD44-TG mice. For up-regulated genes, Mid1, Ttr and Cd4 were significantly up-regulated in the C57△CD44 mouse compared with the C57 mouse, and Pcp2, Ppp1r17 and Nrk were significantly up-regulated in the C57△CD44-TG mouse compared with the C57-TG mouse. As to down-regulated genes, AC114588.1, Cbln3 and Pmch were significantly down-regulated in the C57△CD44 the mouse compared with the C57 mouse, and down-regulated genes were enriched for immunoglobulins, major histocompatibility complex (MHC) class II antigens, chemokines ligands and interferon (IFN)-inducible GTPase families in the C57△CD44-TG mouse compared with the C57-TG mouse. The present study is the first trial for exploring the function of CD44 in the mouse brain during chronic infection with T. gondii at the transcriptional level, which can provide a basis for the study of the host immune defense mechanism against T. gondii infection.

Keywords: CD44; Chronic infection; Mouse; Toxoplasma gondii; Transcriptome analysis.