Genetically resistant mice lacking IL-18 gene develop Th1 response and control cutaneous Leishmania major infection.
IL-18 has been shown to play a critical role in the development of a Th1 response and immunity against intracellular pathogens. To determine the role of IL-18 in the development of protective immunity against Leishmania major, we have analyzed the course of cutaneous L. major in IL-18-deficient C57BL/6 mice (IL-18-/-) compared with similarly infected wild-type mice (IL-18+/+). After L. major infection, IL-18-/- mice may develop larger lesions during early phase of infection but eventually will resolve them as efficiently as IL-18+/+ mice. By 2 wk after infection, although Ag-stimulated lymph node cells from L. major-infected IL-18+/+ and IL-18-/- mice produced similar levels of IFN-gamma, those from IL-18-/- mice produced significantly more IL-12 and IL-4. By 10 wk after infection, both IL-18+/+ and IL-18-/- mice had resolved L. major infection. At this time, lymph node cells from both IL-18+/+ and IL-18-/- mice produced IL-12 and IFN-gamma but no IL-4. Furthermore, administration of anti-IFN-gamma Abs to IL-18-/- mice rendered them susceptible to L. major. These results indicate that despite the role IL-18 may play in early control of cutaneous L. major lesion growth, this cytokine is not critical for development of protective Th1 response and resolution of L. major infection.
Monteforte
G M
GM
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Takeda
K
K
Rodriguez-Sosa
M
M
Akira
S
S
David
J R
JR
Satoskar
A R
AR
D000818:Animals; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020382:Interleukin-18 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma