Dendritic cells (DCs) play a pivotal role in host defense against invaded pathogens including fungi, while DCs are targeted by fungi for deleterious regulation of the host immune response. A few studies have reported fungal modulation of DC function in these immunocompromised AIDS patients. Cryptococcus neoformans (C. neoformans) is referred as one of the opportunistic fungi of AIDS. Here, we isolated native C. neoformans from an AIDS patient and investigated its effects on DC activation and function. Stimulation of C. neoformans matured DCs, and enhanced DC-mediated HIV-1 trans-infection; moreover, C. neoformans-stimulated DCs promoted the activation of resting T cells and provided more susceptible targets for HIV-1 infection. Microbial translocation has been proposed as the cause of systemic immune activation in chronic HIV-1 infection. Understanding the potential effects of pathogens on HIV-1-DC interactions could help elucidate viral pathogenesis and provide a new insight for against the spread of HIV. (C) 2012 Elsevier Inc. All rights reserved.