title: Toxoplasma gondii-infected human myeloid dendritic cells induce T-lymphocyte dysfunction and contact-dependent apoptosis.
abstract: Dendritic cells ignite adaptive immunity by priming naïve T lymphocytes. Human monocyte-derived dendritic cells (MDDCs) infected with Toxoplasma gondii induce T-lymphocyte gamma interferon production and may thus activate T. gondii-specific immunity. However, we now demonstrate that T. gondii-infected MDDCs are poor at activating T lymphocytes and are unable to induce specific cytotoxic T lymphocytes. On the other hand, MDDCs acquiring nonviable T. gondii antigens directly, or indirectly through captured apoptotic or necrotic cell bodies, induce potent T-lymphocyte activation. T lymphocytes exposed to infected MDDCs are significantly impaired in upregulation of CD69 and CD28, are refractory to activation, and die through contact-dependent apoptosis mediated by an as-yet-unidentified mechanism not requiring Fas, tumor necrosis factor-related apoptosis-inducing ligand, leukocyte function antigen 1, intercellular adhesion molecule 1, tumor necrosis factor alpha, interleukin 10, alpha interferon, gamma interferon, prostaglandins, or reactive nitrogen intermediates. Bystander T lymphocytes that were neither infected nor apoptotic were refractory to activation, suggesting global dysfunction. Immunosuppression and T-lymphocyte unresponsiveness and apoptosis are typical of acute T. gondii infection. Our data suggest that infected dendritic cells contribute to these processes. On the other hand, host cells infected with T. gondii are resistant to multiple inducers of apoptosis. Thus, regulation of host cell and bystander cell apoptosis by viable T. gondii may be significant components of a strategy to evade immunity and enhance intracellular parasite survival.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas 75205, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Florentina
authors.initials: F
authors.lastname: Marches
authors.forename: Jozef
authors.initials: J
authors.lastname: Borvak
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Channon
authors.forename: Michael
authors.initials: M
authors.lastname: White
authors.forename: Jay
authors.initials: J
authors.lastname: Radke
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Cesbron-Delauw
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D024201:Bystander Effect; D018106:CD28 Antigens / Q000032:analysis; D002450:Cell Communication; D003713:Dendritic Cells / Q000469:parasitology / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000032:analysis; D007371:Interferon-gamma / Q000502:physiology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D000097802:CD83 Antigen; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; D000099192:CD69 Antigens