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TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.
PLoS One 2013; 8(6):e67036Plos

Abstract

Mother-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-α, IL-10 and IFN-α 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-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α 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-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α 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-α and TNF-α 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-α 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.

Authors+Show Affiliations

Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, Medical School, University of São Paulo, São Paulo, São Paulo, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23826189

Citation

Cardoso, Elaine Cristina, et al. "TLR7/TLR8 Activation Restores Defective Cytokine Secretion By Myeloid Dendritic Cells but Not By Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns." PloS One, vol. 8, no. 6, 2013, pp. e67036.
Cardoso EC, Pereira NZ, Mitsunari GE, et al. TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns. PLoS ONE. 2013;8(6):e67036.
Cardoso, E. C., Pereira, N. Z., Mitsunari, G. E., Oliveira, L. M., Ruocco, R. M., Francisco, R. P., ... Sato, M. N. (2013). TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns. PloS One, 8(6), pp. e67036. doi:10.1371/journal.pone.0067036.
Cardoso EC, et al. TLR7/TLR8 Activation Restores Defective Cytokine Secretion By Myeloid Dendritic Cells but Not By Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns. PLoS ONE. 2013;8(6):e67036. PubMed PMID: 23826189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns. AU - Cardoso,Elaine Cristina, AU - Pereira,Nátalli Zanete, AU - Mitsunari,Gabrielle Eimi, AU - Oliveira,Luanda Mara da Silva, AU - Ruocco,Rosa Maria S A, AU - Francisco,Rossana Pulcineli Vieira, AU - Zugaib,Marcelo, AU - da Silva Duarte,Alberto José, AU - Sato,Maria Notomi, Y1 - 2013/06/27/ PY - 2013/01/23/received PY - 2013/05/14/accepted PY - 2013/7/5/entrez PY - 2013/7/5/pubmed PY - 2013/7/5/medline SP - e67036 EP - e67036 JF - PloS one JO - PLoS ONE VL - 8 IS - 6 N2 - Mother-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-α, IL-10 and IFN-α 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-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α 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-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α 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-α and TNF-α 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-α 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23826189/TLR7/TLR8_Activation_Restores_Defective_Cytokine_Secretion_by_Myeloid_Dendritic_Cells_but_Not_by_Plasmacytoid_Dendritic_Cells_in_HIV_Infected_Pregnant_Women_and_Newborns_ L2 - http://dx.plos.org/10.1371/journal.pone.0067036 DB - PRIME DP - Unbound Medicine ER -