Impairment of thymus-dependent responses by murine dendritic cells infected with foot-and-mouth disease virus.
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-gamma 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-gamma 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.
Ostrowski
Matias
M
Instituto de Virologia, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnologia Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina.
Vermeulen
Monica
M
Zabal
Osvaldo
O
Geffner
Jorge R
JR
Sadir
Ana M
AM
Lopez
Osvaldo J
OJ
D000818:Animals; D039481:CD11b Antigen / Q000235:genetics; D019013:CD40 Antigens / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005536:Foot-and-Mouth Disease / Q000276:immunology; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D014779:Virus Replication
D039481:CD11b Antigen; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II