JNK1 is required for T cell-mediated immunity against Leishmania major infection.
c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays important regulatory roles in helper T cell differentiation. In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice, despite their usually genetically resistant background, were unable to resolve Leishmania infections. Jnk1-/- mice displayed reduced delayed-type hypersensitivity in response to the pathogen, which was associated with a T cell defect. We found that, although these mice can direct an apparent Th1-response, there is also simultaneous generation of Leishmania-specific Th2 responses, which possibly down-modulate protective Th1-mediated immune function. These findings demonstrate that the negative regulation of Th2 cytokine production by the JNK1 signaling pathway is essential for generating Th1-polarized immunity against intracellular pathogens, such as Leishmania major.
Constant
S L
SL
Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute New Haven, CT 06520, USA.
Dong
C
C
Yang
D D
DD
Wysk
M
M
Davis
R J
RJ
Flavell
R A
RA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000469:parasitology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D007111:Immunity, Cellular / Q000235:genetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000469:parasitology; D018417:Th1 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000469:parasitology
D016207:Cytokines; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases