PMID:23826189

Citation	Cardoso, EC, Pereira, NZ, Mitsunari, GE, Oliveira, LM, Ruocco, RM, Francisco, RP, Zugaib, M, da Silva Duarte, AJ and Sato, MN (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:e67036
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.
Links	PubMed PMC3694931 Online version:10.1371/journal.pone.0067036
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TLR2		GO:0001819: interleukin-10 production	ECO:0000314: direct assay evidence used in manual assertion		P		Figure 2A	complete CACAO 9869
HUMAN:TLR9		GO:0032640: tumor necrosis factor production	ECO:0000314:		P		Fiugre 1:Two samples of mononuclear cells were collected, TLR 9 agonist was added in one sample, and absent in another. Levels of TNF Alpha were measured respectively and seen higher when induced with the agonist.	complete CACAO 9868
HUMAN:TLR9	involved_in	GO:0032640: tumor necrosis factor production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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