Indinavir-treated Cryptococcus neoformans promotes an efficient antifungal immune response in immunosuppressed hosts.
A previous paper demonstrated that indinavir affects the virulence of Cryptococcus neoformans, thereby rendering the fungus more susceptible to killing by natural effector cells. This study demonstrates that inoculation of immunosuppressed mice with C. neoformans previously exposed to indinavir, in comparison to untreated C. neoformans, results in: (i) a more pronounced secretion of interleukin-12 by splenic dendritic cells; (ii) reduction of CD14 and Fc gammaRs expression on splenic dendritic cells, and upregulation of CD86 and CD40 molecules; (iii) enhancement of interferon-y and interleukin-2 production by splenic T cells and increase of their proliferation in response to fungal antigens; and (iv) survival from an otherwise lethal challenge, correlated with a drastic decrease in colony forming units from brain and liver. In conclusion, these data indicate that indinavir interaction with C. neoformans could be beneficial because of its direct influence on fungal virulence and blunting of the deleterious effects exerted by C. neoformans on host immune response. Thus, indinavir could be crucial in addressing the outcome of cryptococcosis in immunocompromised hosts.
Pericolini
Eva
E
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Cenci
Elio
E
Monari
Claudia
C
Perito
Stefano
S
Mosci
Paolo
P
Bistoni
Giovanni
G
Vecchiarelli
Anna
A
D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D003453:Cryptococcosis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D016867:Immunocompromised Host; D019469:Indinavir / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology
D051940:B7-2 Antigen; D019013:CD40 Antigens; C485701:Fcgr1 protein, mouse; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D018664:Interleukin-12; D009569:Nitric Oxide; D019469:Indinavir; D007371:Interferon-gamma