title: PPE38 Protein ofMycobacterium tuberculosisInhibits Macrophage MHC Class I Expression and Dampens CD8+T Cell Responses.
abstract: Suppression of CD8+T cell activation is a critical mechanism used byMycobacterium tuberculosis(MTB) to escape protective host immune responses. PPE38 belongs to the unique PPE family of MTB and in our previous study, PPE38 protein was speculated to participate in manipulating macrophage MHC class I pathway. To test this hypothesis, the function of mycobacterial PPE38 protein was assessed here using macrophage and mouse infection models. Decreased amount of MHC class I was observed on the surface of macrophages infected with PPE38-expressing mycobacteria. The transcript of genes encoding MHC class I was also inhibited by PPE38. After infection of C57BL/6 mice withMycobacterium smegmatisexpressing PPE38 (Msmeg-PPE38), decreased number of CD8+T cells was found in spleen, liver, and lungs through immunohistochemical analysis, comparing to the control strain harboring empty vector (Msmeg-V). Consistently, flow cytometry assay showed that fewer effector/memory CD8+T cells (CD44highCD62Llow) were activated in spleen from Msmeg-PPE38 infected mice. Moreover, Msmeg-PPE38 confers a growth advantage over Msmeg-V in C57BL/6 mice, indicating an effect of PPE38 to favor mycobacterial persistencein vivo. Overall, this study shows a unique biological function of PPE38 protein to facilitate mycobacteria to escape host immunity, and provides hints for TB vaccine development.
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Meng
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University Shanghai, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Tong
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan UniversityShanghai, China; The State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, School of Medicine, Shenzhen UniversityGuangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences Shanghai, China.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Tao
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University Shanghai, China.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Niu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D057131:Immune Evasion; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020102:Mycobacterium smegmatis / Q000276:immunology / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology
chemical_list: D015395:Histocompatibility Antigens Class I
keywords: CD8+ T cells; MHC class I; Mycobacterium; PPE38; macrophages