No abstract

Adaptive immune responses are acknowledged to evolve from innate immunity. However, limited information exists regarding whether encounters between innate cells direct the generation of specialized T-cell subsets. We aim to understand how natural killer (NK) cells modulate cell-mediated immunity in humans. We found that human CD14+CD16− monocytes that differentiate into inflammatory dendritic cells (DCs) are shaped at the early stages of differentiation by cell-to-cell interactions with NK cells. Although a fraction of monocytes is eliminated by NK-cell–mediated cytotoxicity, the polarization of interferon-γ (IFN-γ) at the NKp30-stabilized synapses triggers a stable IFN-γ signature in surviving monocytes that persists after their differentiation into DCs. Notably, NK-cell–instructed DCs drive the priming of type 17 CD8+ T cells (Tc17) with the capacity to produce IFN-γ and interleukin-17A. Compared with healthy donors, this cellular network is impaired in patients with classical NK-cell deficiency driven by mutations in the GATA2 gene. Our findings reveal a previously unrecognized connection by which Tc17-mediated immunity might be regulated by NK-cell–mediated tuning of antigen-presenting cells.

Schinus terebinthifolius Raddi is a well-known medicinal plant native of South America. This species has demonstrated important biological activities such as antihypertensive and vasodilator, antimicrobial, anti-inflammatory and antioxidant. However, no studies have been, so far, reported with the fruits of S. terebinthifolius as a protector of the placenta against Zika virus infection and as sunscreen agents. The present study aimed to investigate new uses for the ethanolic fruit extracts of S. terebinthifolius, from fruits'peel (STPE) and from the whole fruits (STWFE). Zika virus (ZIKV) has been linked to several fetal malformations, such as microcephaly and other central nervous system abnormalities. Thus, the potential of these natural extracts against ZIKV infection was evaluated, using an in vitro method. The photoprotective potential, determined by spectrometry, along with phenolic content, antioxidant capacity, and chemical composition of both extracts were also evaluated. The chemical composition of the extracts was evaluated by HPLC-UV / vis. The cytotoxicity of peel and whole fruit extracts in vero E6 cell lines, in placental cell lines and placental explant cultures were evaluated by the MTT assay. The infectivity of placental cells and explants was evaluated by qRT-PCR and the effects of extracts on ZIKV infection were investigated using HTR-8/SVneo cells, pre-treated with 100 μg mL −1 of STWFE for 1 h, and infected with MR766 (AD) or PE243 (EH) ZIKV strains. STFE and STWFE were well-tolerated by both placental-derived trophoblast cell line HTR-8/SVneo as well as by term placental chorionic villi explants, which indicate absence of cytotoxicity in all analysed concentrations. Two strains of ZIKV were tested to access if pretreatment of trophoblast cells with the STWFE would protect them against infection. Flow cytometry analysis revealed that STWFE extract greatly reduced ZIKV infection. The extracts were also photoprotective with SPF values equivalent to the standard, benzophenone-3. The formulations prepared in different concentrations of the extracts (5-10 %) had shown maximum SPF values of 32.21. STWFE represents a potential natural mixture to be used in pregnancy in order to restrain placental infection by ZIKV and might potentially protect fetus against ZIKV-related malformations. The extracts exhibited photoprotective activity and some of the phenolic compounds, mainly resveratrol, catechin and epicatechin, are active ingredients in all assayed activities. The development of biotechnological/medical products, giving extra value to products from family farming, is expected, with strong prospects for success.

Group B Streptococcus (GBS) infection during pregnancy is involved in maternal sepsis, chorioamnionitis, prematurity, fetal infection, neonatal sepsis, and neurodevelopmental alterations. The GBS-induced chorioamnionitis leads to a plethora of immune and trophoblast cells alterations that could influence endothelial cells to respond differently to angiogenic mediators and alter placental vascular structure and function in pregnant women. In this context, preventive measures are needed to reduce such dysfunctions. As such, we evaluated the effects of a non-lethal exposure to inactivated GBS on trophoblast cells and chorionic villi explants, and if the treatment with uvaol would mitigate these effects. The concentration of 106 CFU of GBS was chosen since it was unable to reduce the HTR-8/SVneo cell line nor term chorionic villi explant viability. Raman spectroscopy of trophoblast cells showed significant alterations in their biochemical signature, mostly reverted by uvaol. GBS exposure increased HTR-8/SVneo cells IL-1β and IFN-γ production, phagocytosis, oxidative stress, and decreased trophoblast cell migration. The Ea.hy926 endothelial cell line produced angiopoietin-2, CXCL-8, EGF, FGF-b, IL-6, PlGF, sPECAM-1, and VEGF in culture. When co-cultured in invasion assay with HTR-8/SVneo trophoblast cells, the co-culture had increased production of angiopoietin-2, CXCL-8, FGF-b, and VEGF, while reduced sPECAM-1 and IL-6. GBS exposure led to increased CXCL-8 and IL-6 production, both prevented by uvaol. Chorionic villi explants followed the same patterns of production when exposed to GBS and response to uvaol treatment as well. These findings demonstrate that, even a non-lethal concentration of GBS causes placental inflammation and oxidative stress, reduces trophoblast invasion of endothelial cells, and increases CXCL-8 and IL-6, key factors that participate in vascular dysregulation observed in several diseases. Furthermore, uvaol treatment prevented most of the GBS-provoked changes. Hence, uvaol could prevent the harmful effects of GBS infection for both the mother and the fetus.