title: Modulation of CD11C+ splenic dendritic cell functions in murine visceral leishmaniasis: correlation with parasite replication in the spleen.
abstract: BALB/c mice resolve Leishmania donovani infection in the liver over an 8-12-week period. However, after an initial phase of 2-4 weeks where increases in parasite load are not readily detectable, parasite numbers in the spleen begin to increase reaching maximum levels at 16 weeks post-infection. Thereafter, parasite replication in the spleen is controlled and BALB/c mice maintain this residual parasite load in the spleen for many months, without further increase. We evaluated functions of CD11C+ splenic dendritic cells throughout the course of L. donovani infection in the spleen of BALB/c mice. Unlike the dendritic cell (DC)-specific antigen DEC-205, CD11C was not up-regulated on macrophages during visceral leishmaniasis. No appreciable impairment of splenic DC functions was observed when this antigen-presenting cell subset was purified from 30-day post-infected mice. Significant impairment in inducing allogeneic mixed lymphocyte reaction (MLR) and presenting L. donovani antigens or keyhole limpet haemocyanin (KLH) to specific T cells was observed with CD11C+ splenic DC purified from 60-day post-infected mice. Functional impairment of splenic DC at 60 days post-infection correlated with their reduced surface expression of major histocompatibility complex (MHC) class II molecules, impairment of interleukin-12 (IL-12) production and to their ability to suppress interferon-gamma (IFN-gamma) production by Leishmania antigen-primed T cells. Of interest, the impairment of splenic DC in presenting Leishmania antigens or KLH to specific T cells was corrected at 120 days post-infection, and correlated with their up-regulation of MHC class II expression, IL-12 production, induction of IFN-gamma by Leishmania antigen-primed T cells and the onset of control over splenic parasite replication in vivo. These results indicate that functional integrity of DC may be important in controlling L. donovani infection.
authors.affiliation: Indian Institute of Chemical Biology, Calcutta, India.
authors.forename: A
authors.initials: A
authors.lastname: Basu
authors.forename: G
authors.initials: G
authors.lastname: Chakrabarti
authors.forename: A
authors.initials: A
authors.lastname: Saha
authors.forename: S
authors.initials: S
authors.lastname: Bandyopadhyay
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016167:Integrin alphaXbeta2 / Q000032:analysis*; D018664:Interleukin-12 / Q000378:metabolism; D007893:Leishmania donovani / Q000254:growth & development*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology* / Q000469:parasitology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D018664:Interleukin-12