ROSA MARIA DE SOUZA AVEIRO RUOCCO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
4 resultados
Resultados de Busca
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- Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers(2013) PEREIRA, Natalli Zanete; CARDOSO, Elaine Cristina; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; BRANCO, Anna Claudia Calvielli Castelo; RUOCCO, Rosa Maria de Souza Aveiro; ZUGAIB, Marcelo; OLIVEIRA FILHO, Joao Bosco de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiPrograms for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5 alpha (TRIM-5 alpha), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-beta, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and alpha-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5 alpha protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-beta mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.
conferenceObject UPREGULATION OF ANTIVIRAL FACTORS EXPRESSION BY LIGANDS OF TOLL-LIKE RECEPTORS IN CORD BLOOD OF HIV-INFECTED MOTHERS(2015) PEREIRA, N. Z.; MANFRERE, K. C. G.; BRANCO, A. C. C. C.; RUOCCO, R. M. S. A.; DUARTE, A. J. S.; SATO, M. N.- TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns(2013) CARDOSO, Elaine Cristina; PEREIRA, Natalli Zanete; MITSUNARI, Gabrielle Eimi; OLIVEIRA, Luanda Mara da Silva; RUOCCO, Rosa Maria S. A.; FRANCISCO, Rossana Pulcineli Vieira; ZUGAIB, Marcelo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiMother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-alpha, IL-10 and IFN-alpha secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-alpha production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-alpha response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-alpha secretion in both maternal and CB cells in the infected group. An increase in IFN-alpha secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-alpha and TNF-alpha in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-alpha secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway could function as an adjuvant to improve maternal-neonatal innate immunity.
conferenceObject Impaired APOBEC3G and TRIM-5 alpha expression in decidual and villi tissue of mothers infected by HIV-1(2013) PEREIRA, N. Z.; CARDOSO, E. C.; MITSUNARI, G. E.; RUOCCO, R. M. S. A.; ZUGAIB, M.; OLIVEIRA-FILHO, J. B.; DUARTE, A. J. S.; SATO, M. N.Background: A high percentage of infants from mothers infected by HIV-1 was uninfected even in the absence of antiretroviral therapy. The purpose of this study was to evaluate the expression of antiviral factors in HIV-infected mothers and cord blood (CB), compared with uninfected mothers-CB. Methods: The antiviral factors were evaluated in PBMC, decidual and placental villi tissue. The study was approved by the ethics committee of no 0034/11. Results: High mRNA of antiviral factors was detectable in PBMC of HIV-infected mothers-CB. Furthermore, despite of normal transcriptional APOBEC3G and TRIM-5α, the protein expression was significantly decreased in decidual and villi tissue, respectively, in HIV-infected mothers compared to control mothers. Conclusion: HIV infection may induce an impairment of antiviral factors at post-transcriptional levels at the maternal-fetal interface, with an enhancement of these factors at peripheral blood.