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Impairment of Thymus-Dependent Responses by Murine Dendritic Cells Infected with Foot-and-Mouth Disease Virus¹

Matias Ostrowski^*,, Monica Vermeulen^,, Osvaldo Zabal^*, Jorge R. Geffner^,, Ana M. Sadir^*, and Osvaldo J. Lopez^2,

^* Instituto de Virologia, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnologia Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina; and Department of Biology, Northern Michigan University, Marquette, MI 49855

Foot-and-mouth disease virus (FMDV) is a cytopathic virus that experimentally infects mice, inducing a thymus-independent neutralizing Ab response that rapidly clears the virus. In contrast, vaccination with UV-inactivated virus induces a typical thymus-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 and up-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 and splenocytes. High quantities of these cytokines are also detected in the spleens of FMDV-infected mice, but not in the spleens of vaccinated mice. The peak secretion of IFN- and IL-10 is concurrent with the suppression of Con A-mediated proliferation of T cells obtained from the spleens of infected mice. Furthermore, the secretion of these cytokines correlates with the suppression of the response to OVA, a typical TD Ag. Thus, infection of DCs with FMDV induces suppression of TD responses without affecting the induction of a protective thymus-independent response. Later, T cell responses are restored, setting the stage for the development of a long-lasting protective immunity.

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