c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection
Authors
Pedra, Joao H.F.Mattner, Jochen
Tao, Jian
Kerfoot, Steven M.
Davis, Roger J.
Flavell, Richard A.
Askenase, Philip W.
Yin, Zhinan
Fikrig, Erol
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2008-01-01Keywords
Gamma interferonAnaplasma phagocytophilum infection
c-Jun NH2-terminal kinase 2 (JNK2)
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Immunity
Immunology of Infectious Disease
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
Infect Immun. 2008 Jan;76(1):308-16. Epub 2007 Nov 12. Link to article on publisher's siteDOI
10.1128/IAI.00599-07Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28335PubMed ID
17998313Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.ae974a485f413a2113503eed53cd6c53
10.1128/IAI.00599-07