UMMS Affiliation
Program in Molecular Medicine
Publication Date
2008-01-01
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunity | Immunology of Infectious Disease | Molecular Biology
Abstract
Gamma interferon (IFN-gamma) plays a critical role in the early eradication of Anaplasma phagocytophilum. However, the mechanisms that regulate IFN-gamma production upon infection remain poorly understood. Here we show that c-Jun NH2-terminal kinase 2 (JNK2) inhibits IFN-gamma production during A. phagocytophilum infection. jnk2-null mice were more refractory to infection with A. phagocytophilum and produced increased levels of IFN-gamma after challenge with the pathogen. The resistance of jnk2-null mice to A. phagocytophilum infection was due to elevated levels of IFN-gamma secreted by conventional and natural killer (NK) T cells. The administration of alpha-galactosylceramide, a strong NK T-cell agonist, increased IFN-gamma release and protected mice from A. phagocytophilum, further demonstrating the inhibitory effect of JNK2 on IFN-gamma production. Collectively, these findings provide strong evidence that JNK2 is an important regulatory protein for IFN-gamma secretion upon challenge with A. phagocytophilum.
Keywords
Gamma interferon, Anaplasma phagocytophilum infection, c-Jun NH2-terminal kinase 2 (JNK2)
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
DOI of Published Version
10.1128/IAI.00599-07
Source
Infect Immun. 2008 Jan;76(1):308-16. Epub 2007 Nov 12. Link to article on publisher's site
Journal/Book/Conference Title
Infection and immunity
Related Resources
PubMed ID
17998313
Repository Citation
Pedra, Joao H.F.; Mattner, Jochen; Tao, Jian; Kerfoot, Steven M.; Davis, Roger J.; Flavell, Richard A.; Askenase, Philip W.; Yin, Zhinan; and Fikrig, Erol, "c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection" (2008). Davis Lab Publications. 61.
https://escholarship.umassmed.edu/davis/61
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