Susceptibility to Leishmania mexicana infection is due to the inability to produce IL-12 rather than lack of IL-12 responsiveness.
Almost all inbred mice are highly susceptible to parasites of the Leishmania mexicana complex that includes L. amazonensis and L. mexicana. Recent studies have reported that T cells from L. amazonensis-infected mice fail to respond to IL-12 due to impaired IL-12R expression. Here, we demonstrate that lymph node cells from L. mexicana-infected C57BL/6 and 129Sv/Ev mice respond efficiently to exogenous IL-12 in vitro and produce IFN-gamma. Moreover, we also show that deletion of signal transducer and activator of transcription (STAT)4 gene in resistant STAT6-/- mice renders them susceptible to L. mexicana. These findings indicate that an inability to produce IL-12 rather than unresponsiveness to this cytokine is responsible for susceptibility to L. mexicana. Moreover, the data also demonstrate that the STAT4-mediated pathway is critical for the development of protective immunity against cutaneous leishmaniasis, regardless of the species of Leishmania and/or genetic background of the mice.
Rodriguez-Sosa
M
M
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
Monteforte
G M
GM
Satoskar
A R
AR
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004198:Disease Susceptibility; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology*; D007894:Leishmania mexicana / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma