1. Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain
- Author
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Andrea M. Cooper, Manuela Flórido, António G. Castro, Margarida Borges, Mariana Resende, Ana R. Ribeiro, Marcos S. Cardoso, Nuno L. Alves, Rui Appelberg, Instituto de Investigação e Inovação em Saúde, and Universidade do Minho
- Subjects
0301 basic medicine ,Nitric Oxide Synthase Type II/immunology ,Myeloid ,Mycobacterium avium/growth & development ,Liver cytology ,Nitric Oxide Synthase Type II/biosynthesis ,medicine.medical_treatment ,Medicina Básica [Ciências Médicas] ,Nitric Oxide Synthase Type II ,Macrophages/immunology ,Mice ,0302 clinical medicine ,Liver/immunology ,Spleen/cytology ,Immunology and Allergy ,Interferon gamma ,IL-2 receptor ,Interleukin Receptor Common gamma Subunit/deficiency ,Nitric Oxide Synthase Type II/genetics ,Granuloma/immunology ,Thy-1 Antigens/immunology ,Granuloma ,Innate lymphoid cell ,Interleukin Receptor Common gamma Subunit/genetics ,Antibodies, Monoclonal ,Liver/microbiology ,3. Good health ,DNA-Binding Proteins ,Killer Cells, Natural ,Haematopoiesis ,Cytokine ,medicine.anatomical_structure ,Liver ,Killer Cells, Natural/immunology ,Ciências Médicas::Medicina Básica ,Thy-1 Antigens/genetics ,medicine.drug ,Leukocyte Common Antigens/immunology ,Interleukin Receptor Common gamma Subunit ,Spleen/immunology ,Immunology ,Liver/cytology ,chemical and pharmacologic phenomena ,Biology ,Antibodies, Monoclonal/administration & dosage ,03 medical and health sciences ,Immunocompromised Host ,Interferon-gamma ,Interferon-gamma/biosynthesis ,medicine ,Animals ,Immunocompromised Host/immunology ,DNA-Binding Proteins/immunology ,Granuloma/microbiology ,Interferon-gamma/genetics ,Interleukin Receptor Common gamma Subunit/immunology ,Science & Technology ,Lineage markers ,Hematopoietic Stem Cells/immunology ,Macrophages ,Hematopoietic Stem Cells ,Molecular biology ,Immunity, Innate ,Leukocyte Common Antigens/genetics ,Mice, Inbred C57BL ,030104 developmental biology ,Interferon-gamma/immunology ,Leukocyte Common Antigens ,Thy-1 Antigens ,DNA-Binding Proteins/deficiency ,Mycobacterium avium/immunology ,DNA-Binding Proteins/genetics ,Spleen ,030215 immunology ,Mycobacterium avium - Abstract
IFN-gamma is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-gamma reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-gamma-producing cells of hematopoietic origin that were characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and NK lineage markers. The expression of IFN-g by this population was higher in the liver and lower in the spleen. Furthermore, these cells were present in mice lacking both the Rag2 and the common gamma-chain (gamma c) genes (Rag2(-/-) gamma c(-/-)), indicating their innate nature and their gc cytokine independence. Rag2(-/-) gamma c(-/-) mice are as resistant to Mycobacterium avium as Rag2(-/-) mice, whereas Rag2(-/-) mice lacking IFN-g are more susceptible than either Rag2(-/-) or Rag2(-/-) gamma c(-/-). These lineage-negative CD45(+)/Thy1.2(+) cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2(-/-) gamma c(-/-) animals and are adjacent to macrophages that expressed inducible NO synthase, suggesting a potential protective role for these IFN-gamma-producing cells. Accordingly, Thy1.2specific mAb administration to infected Rag2(-/-) gamma c(-/-) animals increased M. avium growth in the liver. Overall, our results demonstrate that a population of Thy1.2(+) non-NK innate-like cells present in the liver expresses IFN-g and can confer protection against M. avium infection in immunocompromised mice., Supported by a structured program on bioengineered therapies for infectious diseases and tissue regeneration (Grant NORTE-01-0145-FEDER-000012) supported by Norte Portugal Regional Operational Programme (NORTE 2020, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund); by Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation, Portugal 2020; by Portuguese funds through Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (Grant POCI-01-0145-FEDER-007274); by the Trudeau Institute, Inc.; and by FCT Grant SFRH/BD/89871/2012 (to M.R.), info:eu-repo/semantics/publishedVersion
- Published
- 2017