Amastigote load and cell surface phenotype of infected cells from lesions and lymph nodes of susceptible and resistant mice infected with Leishmania major.
Cells of the dendritic cell (DC) lineage, by their unique ability to stimulate naive T cells, may be of crucial importance in the development of protective immune responses to Leishmania parasites. The aim of this study was to compare the impact of L. major infection on DCs in BALB/c (susceptible, developing Th2 responses), C57BL/6 (resistant, developing Th1 responses), and tumor necrosis factor (TNF)(-/-) C57BL/6 mice (susceptible, developing delayed and reduced Th1 responses). We analyzed by immunohistochemistry the phenotype of infected cells in vivo. Granulocytes (GR1(+)) and macrophages (CD11b(+)) appear as the mainly infected cells in primary lesions. In contrast, cells expressing CD11c, a DC specific marker, are the most frequently infected cells in draining lymph nodes of all mice tested. These infected CD11c(+) cells harbored a particular morphology and cell surface phenotype in infected C57BL/6 and BALB/c mice. CD11c(+) infected cells from C57BL/6 and TNF(-/-) C57BL/6 mice displayed a weak parasitic load and a dendritic morphology and frequently expressed CD11b or F4/80 myeloid differentiation markers. In contrast, some CD11c(+) infected cells from BALB/c mice were multinucleated giant cells. Giant cells presented a dramatic accumulation of parasites and differentiation markers were not detectable at their surface. In all mice, lymph node CD11c(+) infected cells expressed a low major histocompatibility complex II level and no detectable CD86 expression. Our results suggest that infected CD11c(+) DC-like cells might constitute a reservoir of parasites in lymph nodes.
Muraille
Eric
E
Laboratory of Parasitology, Université Libre de Bruxelles, Erasme, Brussels, Belgium.
De Trez
Carl
C
Pajak
Bernard
B
Torrentera
Fabiola Aguilar
FA
De Baetselier
Patrick
P
Leo
Oberdan
O
Carlier
Yves
Y
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D051940:B7-2 Antigen; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology*; D004198:Disease Susceptibility; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007150:Immunohistochemistry; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype
D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins