c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection.
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.
Pedra
Joao H F
JH
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Mattner
Jochen
J
Tao
Jian
J
Kerfoot
Steven M
SM
Davis
Roger J
RJ
Flavell
Richard A
RA
Askenase
Philip W
PW
Yin
Zhinan
Z
Fikrig
Erol
E
D041081:Anaplasma phagocytophilum; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016873:Ehrlichiosis / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D017353:Gene Deletion; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D007371:Interferon-gamma; D048056:Mitogen-Activated Protein Kinase 9