The outcome of the parasitic process initiated by Leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the Lsh and MHC loci.
Human visceral leishmaniasis is mainly due to intracellular protozoan parasites of the Leishmania donovani complex, i.e., L. donovani and L. infantum (or L. chagasi). A mouse model has been established to monitor 1) the parasitic process initiated by L. infantum in three tissues they invade, and 2) parameters of the acquired immune response they trigger. Mice congenic at the Lsh locus and mice of inbred strains differing at the MHC locus have been inoculated by the i.v. route with L. infantum. The parasitic process has been evaluated by the follow-up of the parasitic load in the liver, the spleen, and, for the first time, in the bone marrow using a very sensitive limiting dilution assay. As previously established for L. donovani, the early outcome of L. infantum is also under the control of the Lsh locus in the liver; genes of the MHC complex are involved in the development of the subsequent acquired immune response. "Cure" or "noncure" haplotypes are the same for the two species of Leishmania; as far as the cure haplotype is concerned, whatever the tissues being screened, the parasites are never totally cleared, although the liver is the tissue in which the best parasite load reduction is achieved. Through immunostaining, it was established that sialoadhesin-positive stromal bone marrow macrophages contain parasites; such long-lived mononuclear phagocytes could be the host cells where the parasite can find "safe targets" unreactive to the dominant effector immune mechanism triggered by the replicative stage of the parasites.
Leclercq
V
V
Unit of Cellular Immunophysiology, Pasteur Institute, Paris, France.
Lebastard
M
M
Belkaid
Y
Y
Louis
J
J
Milon
G
G
D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D027682:Cation Transport Proteins; D005260:Female; D033862:Iron-Binding Proteins; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000209:etiology* / Q000235:genetics / Q000469:parasitology*; D008109:Liver Diseases, Parasitic / Q000469:parasitology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D013158:Splenic Diseases / Q000469:parasitology; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2