RESUMO
Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-ß1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age.
Assuntos
Idade Gestacional , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Placenta/metabolismo , Placenta/parasitologia , Toxoplasma/fisiologia , Toxoplasmose/parasitologia , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismo , Feminino , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Oxirredutases Intramoleculares/biossíntese , Oxirredutases Intramoleculares/farmacologia , Fatores Inibidores da Migração de Macrófagos/biossíntese , Fatores Inibidores da Migração de Macrófagos/farmacologia , Modelos Biológicos , Nitritos/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Toxoplasma/citologia , Toxoplasma/efeitos dos fármacos , Toxoplasmose/patologia , Toxoplasmose/prevenção & controleRESUMO
The cytokine macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of inflammatory and infectious diseases, however its role in HIV-1 infection is unknown. Here we show that HIV-1-infected patients present elevated plasma levels of MIF, that HIV-1-infected peripheral blood mononuclear cells (PBMCs) release a greater amount of MIF, and that the HIV-1 envelope glycoprotein gp120 induces MIF secretion from uninfected PBMCs. The HIV-1 replication in PBMCs declines when these cells are treated with anti-MIF antibodies, and exposure of HIV-1-infected cells to the ABC-transporter inhibitor probenecid results in inhibition of MIF secretion. The addition of recombinant MIF (rhMIF) to HIV-1-infected PBMCs enhances viral replication of CCR5- or CXCR4-tropic HIV-1 isolates. Using a T CD4(+) cell lineage containing an HIV long terminal repeats (LTR)-Luciferase construct, we detected that rhMIF promotes transcription from HIV-1 LTR. Our results show that HIV-1 induces MIF secretion and suggest that MIF influences the HIV-1 biology through activation of HIV-1 LTR.
Assuntos
Infecções por HIV/virologia , HIV-1 , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Replicação Viral/fisiologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Linhagem Celular , Proteína gp120 do Envelope de HIV/fisiologia , Infecções por HIV/sangue , Repetição Terminal Longa de HIV/fisiologia , Humanos , Oxirredutases Intramoleculares/biossíntese , Leucócitos Mononucleares/fisiologia , Fatores Inibidores da Migração de Macrófagos/biossíntese , Probenecid/farmacologia , Proteínas RecombinantesRESUMO
The present report analyzes the suppressor cell system of aged rats in an experimental model of autoimmunity to rat male accessory glands (RAG). A state of specific suppression to RAG was induced when young rats are pretreated with peritoneal cells (PC) obtained from syngeneic young rats i.p. injected 2 h previously with chromatographic fraction I (Sephadex G-100) (FI) of RAG (yFI-PC). Although the yFI-PC injection diminished the DTH in aged rats the autoimmune response remained positive. Peritoneal cells obtained from aged rats injected with FI of RAG (oFI-PC) did not suppress the DTH response in either aged or young rats. In both young and aged, pretreatment with yFI-PC stimulates spleen cells capable of inducing suppression (inductor-phase suppressor cells) when they are transferred to young recipients. However, the spleen inductor-phase suppressor cells of 12-month-old rats are unable to suppress the autoimmune response in their own aged environment. To obtain effective suppression in 12-month-old rats, the injection of yFI-PC was necessary prior to and subsequent to immunization. In this work we observe that 12-month-old rats could efficiently induce inducer phase and effector-phase suppressor cells when the adequate young antigen-presenting cells were present to stimulate them.
Assuntos
Envelhecimento/fisiologia , Células Apresentadoras de Antígenos/fisiologia , Autoimunidade/fisiologia , Genitália Masculina/imunologia , Animais , Formação de Anticorpos , Transplante de Células , Hipersensibilidade Tardia/imunologia , Fatores Inibidores da Migração de Macrófagos/biossíntese , Masculino , Peritônio/citologia , Ratos , Ratos WistarRESUMO
A model of autoimmunity to rat male accessory glands (RAG) was recently developed by intraperitoneal administration of three doses of native RAG associated with liposomes. In this work we analysed the effects of gangliosides in the cellular response to RAG when they were intraperitoneally administrated prior to the second dose of liposome-associated RAG. Results show that the ganglioside treatment could modify an established DTH response. Also, gangliosides markedly reduced the number of Ia antigen-positive peritoneal exudated cells (PEC). However, they modified neither the processing of liposomes through PEC nor their viability. Moreover, we obtained cellular response by transferring PEC from immunized donors into naive receptors.
Assuntos
Autoimunidade/efeitos dos fármacos , Gangliosídeos/farmacologia , Genitália Masculina/imunologia , Lipossomos/imunologia , Macrófagos Peritoneais/imunologia , Animais , Antígenos de Superfície/efeitos dos fármacos , Feminino , Hipersensibilidade Tardia/diagnóstico , Fatores Inibidores da Migração de Macrófagos/biossíntese , Macrófagos Peritoneais/transplante , Masculino , Microscopia de Fluorescência , Fagocitose/fisiologia , Ratos , Ratos Endogâmicos , Ratos WistarRESUMO
The ability of conidia, the infectious form of the dimorphic fungus Paracoccidioides brasiliensis, to be killed in vitro by murine pulmonary macrophages was studied. Mice were immunized by intravenous injection of killed conidia, which resulted in cellular immunity demonstrated by delayed type hypersensitivity in vivo and macrophage migration inhibition factor production in vitro. Resident pulmonary macrophages from non-immune mice were able to significantly kill the conidia (28%). Such macrophages treated with supernatants (cytokines) from antigen-stimulated immune mononuclears had a markedly enhanced ability to kill conidia (73%). These results show that activated pulmonary macrophages are potent killers of conidia of P. brasiliensis and that immune mononuclears play a role in activation of macrophages. Activated macrophages may be important for pulmonary defense against the initial stages of infection with this fungus.