ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Mice with a selective impairment of IFN-gamma signaling in macrophage lineage cells demonstrate the critical role of IFN-gamma-activated macrophages for the control of protozoan parasitic infections in vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 103 citations in OpenAlex.
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- Axl receptor induces efferocytosis, dampens M1 macrophage responses and promotes heart pathology in Trypanosoma cruzi infection.Communications biology · 2022Article
- Type I IFN Signaling Is Essential for Preventing IFN-γ Hyperproduction and Subsequent Deterioration of Antibacterial Immunity during Postinfluenza Pneumococcal Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- CCR5 maintains macrophages in the bone marrow and drives hematopoietic failure in a mouse model of severe aplastic anemia.Leukemia · 2021Article
- IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome.JCI insight · 2021Article
- Immune response dynamics and Lutzomyia longipalpis exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort.PLoS neglected tropical diseases · 2021Article
- Resistance AgainstFrontiers in immunology · 2021Article
- Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury.Frontiers in immunology · 2021Review
- IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact onFrontiers in immunology · 2021Article
- Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism.Cytokine: X · 2020Article
- Myeloid cell responsiveness to interferon-gamma is sufficient for initial resistance toCurrent research in immunology · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
IFN-gamma has long been recognized as a cytokine with potent and varied effects in the immune response. Although its effects on specific cell types have been well studied in vitro, its in vivo effects are less clearly understood because of its diverse actions on many different cell types. Although control of multiple protozoan parasites is thought to depend critically on the direct action of IFN-gamma on macrophages, this premise has never been directly proven in vivo. To more directly examine the effects of IFN-gamma on cells of the macrophage lineage in vivo, we generated mice called the "macrophages insensitive to IFN-gamma" (MIIG) mice, which express a dominant negative mutant IFN-gamma receptor in CD68+ cells: monocytes, macrophages, dendritic cells, and mast cells. Macrophage lineage cells and mast cells from these mice are unable to respond to IFN-gamma, whereas other cells are able to produce and respond to this cytokine normally. When challenged in vitro, macrophages from MIIG mice were unable produce NO or kill Trypanosoma cruzi or Leishmania major after priming with IFN-gamma. Furthermore, MIIG mice demonstrated impaired parasite control and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an appropriate IFN-gamma response. In contrast, MIIG mice displayed normal control of lymphocytic choriomeningitis virus, despite persistent insensitivity of macrophages to IFN-gamma. Thus, the MIIG mouse formally demonstrates for the first time in vivo, the specific importance of direct, IFN-gamma mediated activation of macrophages for controlling infection with multiple protozoan parasites.
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