Screening of PD-L1 related specific candidate genes in tuberculosis by transcriptome sequencing and analysis in mycobacterium tuberculosis infected pdl1 knockout macrophages

doi:10. 3969 / j.issn.1671-7856. 2020. 05. 006

Home > Archive>Volume 30, Issue 5, 2020 >31-39. DOI:10. 3969 / j.issn.1671-7856. 2020. 05. 006

Screening of PD-L1 related specific candidate genes in tuberculosis by transcriptome sequencing and analysis in mycobacterium tuberculosis infected pdl1 knockout macrophages
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                        10. 3969 / j.issn.1671-7856. 2020. 05. 006
                    
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                        SHI YananSHI Yanan
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
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TANG JunTANG Jun
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
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LI JunliLI Junli
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
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WANG JieWANG Jie
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
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ZHAN LingjunZHAN Lingjun
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
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Affiliation:Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Key Laboratory of Human Diseases Comparative Medicine, National Health Commission of P.R.C; Beijing Key Laboratory of Animal Models of Emerging and Reemerging Infectious Diseases; Research Center of Laboratory Animal Model Engineering and Technology of Human Critical Diseases in Beijing; Tuberculosis Center, CAMS, Beijing 100021, China
Clc Number:R-33
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Abstract:

Objective To analyze the transcription profile of Mycobacterium tuberculosis ( Mtb )-infected macrophages in which the pdl1 gene has been knocked out and screen PD-L1 related candidate genes in Mtb -infected macrophages (MΦ). Methods pdl1^{Flox / -} mice were constructed, and homozygous (pdl1^{Flox / Flox}with Cre) and heterozygous (pdl1^{Flox / -} with Cre) mice with targeted inactivation of the pdl1 gene in MΦs were bred by the Cre / loxP technique and verified by PCR and FACS. Peritoneal MΦs were isolated from different substrains of mice, and those isolated from littermate negative mice (pdl1^{Flox / Flox}) were used as controls. Twenty-four hours after infection, the transcript profiles in the infected and uninfected groups were sequenced by RNA-Seq, and bioinformatics analysis was performed. Results pdl1- specific knockout mice were successfully generated and identified by PCR and FACS. The pdl1^{Flox / Flox}with Cre, pdl1^{Flox / -} with Cre, and pdl1^{Flox / Flox} infected groups were compared with their corresponding non-infected groups. Gene Ontology (GO) functional enrichment analysis showed that the most significant enrichments were immune response (P< 0. 01) and immune system processes (P< 0. 01). The seventeen candidate genes identified were regarded as specific genes related to PD-L1 in Mtb infection. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the most significantly enriched pathways included Toll-like receptor (P< 0. 01) and nuclear factor kappa-B (NF-κB) (P< 0. 01) signaling pathways, and six candidate genes related to PD-L1 were screened. Conclusions Through transcription analysis, seventeen genes related to the immune response, including Ccl2, Qa5, and Il12a, and six genes in immune - and inflammation-related metabolic pathways, including Ptgs2, Cd40, and Card11, were identified as specific candidate genes related to PD-L1 in macrophages infected with Mtb. Except for Il6, all candidate genes were selected for this research.

Key words:Mycobacterium tuberculosis; macrophages; pdl1 gene knockout; Cre / loxP recombinase system; transcriptome sequencing

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Received:December 19,2019
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Online: June 19,2020
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