Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes.
To induce a specific response in primary resting T cells, two signals must be provided by antigen-presenting cells (APC). The first antigen-specific signal is mediated by formation of the T cell receptor major histocompatibility complex molecule ternary complexes. The second signal is delivered by interaction of either B7-1 or B7-2 expressed by APC with CD28 or CTLA-4 on T cells. In this study, we examined the modulation of B7-1 and B7-2 molecules on human monocytes exposed to encapsulated or acapsular Cryptococcus neoformans or Candida albicans. In our experimental system, C. albicans or acapsular C. neoformans are able to induce B7-1 expression while the encapsulated yeast is a poor stimulator. A modest increase of B7-2 expression was also observed after monocyte treatment with acapsular C. neoformans or C. albicans, while the encapsulated yeast was ineffective in inducing B7-2 molecules. Kinetic analysis showed the maximum expression of B7-1 after 24 to 48 h. Addition of the opsonic IgG1 mAb 2H1 to monocytes and C. neoformans significantly increased B7-1, but not B7-2, expression. The contribution of B7-1 and B7-2 co-stimulatory (CS) molecules to cryptococcal-specific T cell activation was analyzed and a substantial inhibition of T cell proliferation was observed. In this study we provide the first demonstration of fungal interference in the regulation of CS molecules. Our results suggest a potential mechanism for poor inflammatory responses observed in C. neoformans infections.
Vecchiarelli
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy. vecchiar@unipg.it
Monari
C
C
Retini
C
C
Pietrella
D
D
Palazzetti
B
B
Pitzurra
L
L
Casadevall
A
A
D017951:Antigen Presentation / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051940:B7-2 Antigen; D002176:Candida albicans / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011134:Polysaccharides / Q000276:immunology; D015398:Signal Transduction
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D011134:Polysaccharides; C014426:cryptococcal polysaccharide