IL-12 gene-deficient C57BL/6 mice are susceptible to Leishmania donovani but have diminished hepatic immunopathology.
To determine the in vivo role of IL-12 in the development of protective immunity in visceral leishmaniasis caused by Leishmania donovani, we examined the course of L. donovani infection in IL-12-deficient C57BL/6 (IL-12-/-) mice. IL-12-/- mice displayed significantly higher parasite burdens in their livers and spleens than wild-type C57BL/6 mice throughout the course of infection. Despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in L. donovani-infected IL-12-/-. Moreover, livers and spleens from IL-12-/- mice displayed significantly less inflammation and poorly formed granulomatous lesions than those from IL-12+/+ mice throughout the course of infection. Antigen-stimulated splenocytes from IL-12-/- mice produced significantly less IFN-gamma but more IL-4 than IL-12+/+ mice. These findings indicate that although endogenous IL-12 is critical for the development of protective immunity to L. donovani, it is also responsible for inducing the significant immunopathology associated with visceral leishmaniasis.
Satoskar
A R
AR
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston 02115, USA. asatoska@hsph.harvard.edu
Rodig
S
S
Telford
S R
SR
Satoskar
A A
AA
Ghosh
S K
SK
von Lichtenberg
F
F
David
J R
JR
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D007893:Leishmania donovani / Q000302:isolation & purification / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D008099:Liver / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma