CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease
Publication Date
May 31, 2016
Journal
PLOS Pathogens
Authors
Shunsuke Sakai, Keith D. Kauffman, Michelle A. Sallin, Arlene H. Sharpe, et al
Volume
12
Issue
5
Pages
e1005667
DOI
https://dx.plos.org/10.1371/journal.ppat.1005667
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005667
Web of Science
000379344500049
Scopus
84973315161
Mendeley
http://www.mendeley.com/research/cd4-t-cellderived-ifn%CE%B3-plays-minimal-role-control-pulmonary-mycobacterium-tuberculosis-infection-act
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{"title"=>"CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease", "type"=>"journal", "authors"=>[{"first_name"=>"Shunsuke", "last_name"=>"Sakai", "scopus_author_id"=>"14020553000"}, {"first_name"=>"Keith D.", "last_name"=>"Kauffman", "scopus_author_id"=>"56096092000"}, {"first_name"=>"Michelle A.", "last_name"=>"Sallin", "scopus_author_id"=>"35590807300"}, {"first_name"=>"Arlene H.", "last_name"=>"Sharpe", "scopus_author_id"=>"7103330473"}, {"first_name"=>"Howard A.", "last_name"=>"Young", "scopus_author_id"=>"57189590432"}, {"first_name"=>"Vitaly V.", "last_name"=>"Ganusov", "scopus_author_id"=>"6602157355"}, {"first_name"=>"Daniel L.", "last_name"=>"Barber", "scopus_author_id"=>"7202972466"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pui"=>"610667659", "pmid"=>"27244558", "doi"=>"10.1371/journal.ppat.1005667", "issn"=>"15537374", "scopus"=>"2-s2.0-84973315161", "sgr"=>"84973315161", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)"}, "id"=>"f95a0c6c-5239-3d55-aad7-dbdc9b3f312a", "abstract"=>"IFN-γ-producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here we show that IFN-γ accounts for only ~30% of CD4 T cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen. Moreover, increasing the IFN-γ-producing capacity of CD4 T cells by ~2 fold exacerbates lung infection and leads to the early death of the host, despite enhancing control in the spleen. In addition, we show that the inhibitory receptor PD-1 facilitates host resistance to Mtb by preventing the detrimental over-production of IFN-γ by CD4 T cells. Specifically, PD-1 suppressed the parenchymal accumulation of and pathogenic IFN-γ production by the CXCR3+KLRG1-CX3CR1- subset of lung-homing CD4 T cells that otherwise mediates control of Mtb infection. Therefore, the primary role for T cell-derived IFN-γ in Mtb infection is at extra-pulmonary sites, and the host-protective subset of CD4 T cells requires negative regulation of IFN-γ production by PD-1 to prevent lethal immune-mediated pathology.", "link"=>"http://www.mendeley.com/research/cd4-t-cellderived-ifn%CE%B3-plays-minimal-role-control-pulmonary-mycobacterium-tuberculosis-infection-act", "reader_count"=>70, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>17, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>4, "Student > Master"=>12, "Student > Bachelor"=>8, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>17, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>4, "Student > Master"=>12, "Student > Bachelor"=>8, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>26, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>23, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>23}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>26}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>6}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Mexico"=>1, "South Africa"=>1, "Australia"=>1, "France"=>1}, "group_count"=>1}

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Scopus | Further Information

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