Mice with a selective impairment of IFN-γ signaling in macrophage lineage cells demonstrate the critical role of IFN-γ activated macrophages for the control of protozoan parasitic infections in vivo1, 2
IFN-γ has long been recognized as a cytokine with potent and varied effects in the immune response. While 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. While control of...
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Veröffentlicht in: | The Journal of immunology (1950) 2009-12, Vol.184 (2), p.877-885 |
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Sprache: | eng |
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Zusammenfassung: | IFN-γ has long been recognized as a cytokine with potent and varied effects in the immune response. While 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. While control of multiple protozoan parasites is thought to depend critically on the direct action of IFN-γ on macrophages, this premise has never been directly proven
in vivo
. In order to more directly examine the effects of IFN-γ on cells of the macrophage lineage
in vivo
, we generated mice called the ‘Macrophages Insensitive to Interferon Gamma’ (MIIG) mice, which express a dominant negative mutant IFN-γ 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-γ while 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-γ. Furthermore, MIIG mice demonstrated impaired parasite control and heightened mortality after
T. cruzi, L. major,
and
Toxoplasma gondii
infection, despite an appropriate IFN-γ response. In contrast, MIIG mice displayed normal control of lymphocytic choriomeningitis virus, despite persistent insensitivity of macrophages to IFN-γ. Thus, the MIIG mouse formally demonstrates for the first time
in vivo
, the specific importance of direct, IFN-γ mediated activation of macrophages for controlling infection with multiple protozoan parasites.
“This is an author-produced version of a manuscript accepted for publication in
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(
The JI
). The American Association of Immunologists, Inc. (AAI), publisher of
The JI
, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by
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; hence, it may differ from the final version published in
The JI
(online and in print). AAI (
The JI
) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at
www.jimmunol.org.
” |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.0902346 |