Cutting edge: early IL-4 production governs the requirement for IL-27-WSX-1 signaling in the development of protective Th1 cytokine responses following Leishmania major infection.
There are conflicting reports on the requirements for the IL-27-WSX-1 pathway in the development of Th type 1 responses and resistance to intracellular pathogens; although early IFN-gamma production and resistance to Leishmania major are impaired in the absence of WSX-1 signaling, WSX-1(-/-) mice generate robust IFN-gamma responses and control infection with other intracellular protozoan pathogens. In this report, we resolve these conflicting observations and demonstrate that, in the absence of IL-4, WSX-1 is not required for early IFN-gamma production and control of L. major. Thus, the requirement for WSX-1 signaling in Th type 1 cell differentiation is restricted to conditions in which IL-4 is produced.
Artis
David
D
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Johnson
Leanne M
LM
Joyce
Karen
K
Saris
Christiaan
C
Villarino
Alejandro
A
Hunter
Christopher A
CA
Scott
Phillip
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016207:Cytokines; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma