Human plasmacytoid dendritic cells elicited different responses after infection with pathogenic or non-pathogenic Junín virus strains

NEGROTTO S; MENA HA; URE AE; JAQUENOD DE GIUSTI C; BOLLATI-FOGOLÍN M; VERMEULEN EM; SCHATTNER M; GOMEZ RM

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2015 vol. 89

0022-538X

The arenavirus Junín (JUNV) is the etiologic agent of Argentina Hemorrhagic Fever (AHF), a disease where type I IFN levels correlate with the prognosis. In addition to cytotoxicity and antigen presenting capacity, plasmacytoid dendritic cells (pDCs), through the production of type I IFN, together with IL-6 and TNFα, regulate T, B, NK, conventional DC and regulatory T cell function, playing a critical role during viral infections. We characterized the JUNV infection of human pDC isolated from peripheral blood. By detecting viral RNA, the infectious virus, and the viral protein NP, we demonstrated that human pDC were susceptible to infection by the attenuated (C#1), and even more, by the virulent (P) JUNV. Although JUNV infection failed to induce cell death, P infection prevented caspase-3 activation and IL-3 deprivation-induced apoptosis. JUNV infection induced the pDC activation and maturation reflected by the increased expression levels of HLA-ABC, HLA-DR, CD86 and CD83, as well as type I IFN. The effect of P was, in all cases, higher compared to C#1. In contrast, C#1 significantly enhanced the expression of the pro-inflammatory cytokines IL-6 and TNF-α, whereas P failed to modify IL-6 levels and even reduced the expression of TNF-α below to control values. Our results demonstrated that human pDC is susceptible to infection by both JUNV strains. However, human pDC elicited a different response after infection with pathogenic or non-pathogenic JUNV strains, suggesting that human pDC infection may participate in the pathogenesis of AHF.