Impairment of Thymus-Dependent Responses by Murine Dendritic Cells Infected with Foot-and-Mouth Disease

OSTROWSKI, M; VERMEULEN, M; ZABAL, O; GEFFNER, O; SADIR, AM; LOPEZ O.J.

JOURNAL OF IMMUNOLOGY

Año: 2005 vol. 175 p. 3971 - 3979

0022-1767

Foot-and-mouth disease virus (FMDV) is a cytopathic virus that experimentally infects mice, inducing a thymus-independentneutralizing Ab response that rapidly clears the virus. In contrast, vaccination with UV-inactivated virus induces a typicalthymus-dependent (TD) response. In this study we show that dendritic cells (DCs) are susceptible to infection with FMDV in vitro,although viral replication is abortive. Infected DCs down-regulate the expression of MHC class II and CD40 molecules andup-regulate the expression of CD11b. In addition, infected DCs exhibit morphological and functional changes toward a macrophage-like phenotype. FMDV-infected DCs fail to stimulate T cell proliferation in vitro and to boost an Ab response in vivo.Moreover, infection of DCs in vitro induces the secretion of IFN-! and the suppressive cytokine IL-10 in cocultures of DCs andsplenocytes. High quantities of these cytokines are also detected in the spleens of FMDV-infected mice, but not in the spleens ofvaccinated mice. The peak secretion of IFN-! and IL-10 is concurrent with the suppression of Con A-mediated proliferation ofT cells obtained from the spleens of infected mice. Furthermore, the secretion of these cytokines correlates with the suppressionof the response to OVA, a typical TD Ag. Thus, infection of DCs with FMDV induces suppression of TD responses without affectingthe induction of a protective thymus-independent response. Later, T cell responses are restored, setting the stage for the developmentof a long-lasting protective immunity.