Differential CD86/B7-2 expression and cytokine secretion induced by Toxoplasma gondii in macrophages from resistant or susceptible BALB H-2 congenic mice.
The influence of the intracellular parasite Toxoplasma gondii on macrophage expression of co-stimulatory molecules was studied. Unlike surface expression of CD80/B7-1, that of CD86/B7-2 is increased in mouse peritoneal macrophages 24 h following exposure to live toxoplasma in vitro. Most CD86 molecules are found on infected cells bearing a maximum parasite load. Consistent with the elevated membrane expression, the quantity of CD86 gene transcript is increased in macrophages infected by T. gondii in vitro or in vivo. CD86 up-regulation contributes to the augmented capacity of parasitized macrophages to present antigen to tuberculin-specific CD4+ T cells as demonstrated by blocking CD86 ligand interaction. T. gondii triggers up-regulation of CD86 in macrophages from BALB/c mice which are resistant to the development of toxoplasmic encephalitis. Infection of macrophages from the susceptible strain BALB.B, however, results in a decreased surface expression of CD86, although the parasite load and intracellular proliferation proved comparable in both macrophages. This differential host cell reaction correlates with disparate profiles in T. gondii-induced cytokine secretion. Upon challenge with toxoplasma, IL-1alpha and tumor necrosis factor (TNF)-alpha are released to a significantly higher extent by BALB/c than by BALB.B macrophages, whereas the latter secrete more IL-12 and IL-10. In BALB.B macrophages, T. gondii-induced IL-10 down-regulates surface expression of CD86, thus indicating an interference of parasite-dependent cytokine release and modulation of CD86. The biased secretory response in macrophages from the two congenic strains implies an MHC-dependent and dichotomous monokine induction by T. gondii. Up-regulation of CD86 seems to occur along the IL-1/TNF-inducing pathway and experimental evidence indicates that this enhances T cell activation by parasitized macrophages.
Fischer
H G
HG
Institute for Medical Microbiology and Virology, Heinrich-Heine-University, Düsseldorf, Germany.
Dörfler
R
R
Schade
B
B
Hadding
U
U
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis*; D051940:B7-2 Antigen; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D006183:H-2 Antigens / Q000235:genetics; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C / Q000235:genetics; D018448:Models, Immunological; D013045:Species Specificity; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D006183:H-2 Antigens; D007378:Interleukins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha