Publisher Correction: TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

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TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria.

Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65GFP infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus.

Salivary epidermal growth factor concentrations in patients with Sjögren syndrome and laryngopharyngeal reflux.

Sjögren syndrome was chosen as a clinical model to study acinar salivary deficiencies in the development of laryngopharyngeal reflux (LPR). The objective of this prospective cohort study was to compare salivary epidermal growth factor (EGF) concentrations of patients with Sjögren syndrome with and without LPR and gastroesophageal reflux disease (GERD) with normal controls. LPR was diagnosed with positive scores on the Reflux Symptom Index and Reflux and Reflux Finding Score, corroborated by esophagogastroduodenoscopy and/or 24-hour pH-metry. Salivary EGF concentrations of both unstimulated and mechanically stimulated saliva were established using enzyme-linked immunosorbent assay, and the significance level was set at 95%. Twenty-one patients and 19 controls were studied. All patients had LPR and 60% also had GERD. The mean salivary EGF concentration of unstimulated and stimulated saliva in the control group was 1,751.37 pg/ml and 544.76 pg/ml, respectively. Unstimulated and stimulated salivary EGF concentrations in the study group were 2,534.65 pg/ml and 920.69 pg/ml, respectively. These differences were not statistically significant. Body mass index, presence of erosive esophagitis, or severity of hyposalivation did not significantly influence salivary EGF concentrations. LPR and GERD are highly prevalent in patients with Sjögren syndrome. Unlike previous studies in which significant EGF deficiencies were found in patients with reflux laryngitis and GERD, patients with Sjögren syndrome seem to have reflux caused by a decrease in clearance capacity and not in specific salivary components.

Astrocytic Expression of the Immunoreceptor CD300f Protects Hippocampal Neurons from Amyloid-ß Oligomer Toxicity In Vitro.

BACKGROUND: Astrocytes contribute to neuroinflammation that accompanies neurodegenerative disorders such as Alzheimer's disease (AD). In this sense, the toxicity of these diseases might be attenuated through the modulation of astrocytic inflammatory responses. Recently, the CD300f immunoreceptor was described as a new member of the CD300 immunoreceptor family, showing promising modulatory properties. OBJECTIVE: Here, we investigated whether overexpression of hCD300f (the human isoform of CD300f) in astrocytes protects hippocampal neurons against the degeneration induced by amyloid-beta (Aß) oligomer. METHOD: Astrocyte monolayers were transfected with hCD300f before seeding the hippocampal neurons, and then the co-culture was exposed to Aß1-42 oligomers (5 µM, 48h). RESULTS: hCD300f expression significantly abrogated the neuronal loss elicited by Aß. This effect was dependent on neuron-astrocyte cell-cell interactions since no protection was observed using conditioned media from transfected astrocytes. Astrocyte modulation was dependent on the cytoplasmic signaling tail of hCD300f. Furthermore hCD300f expression did not affect the ability of astrocytes to uptake Aß1- 42 oligomers by endocytosis, which discards the possibility that increased Aß1-42 clearance could mediate neuroprotection by hCD300f. CONCLUSION: These results suggest that the astrocyte-directed expression of the hCD300f immune receptor can be a neuroprotective strategy in AD disease.

Salivary concentration of epidermal growth factor in adults with reflux laryngitis before and after treatment.

OBJECTIVES: The diagnosis of laryngopharyngeal reflux (LPR) is controversial. There is no correlation between the number of reflux episodes and the severity of the inflammatory response at the esophagus or the laryngopharyngeal segment. Some authors have suggested that decreased salivary epidermal growth factor (EGF) concentrations in patients with gastroesophageal reflux disease and LPR point to a breakdown in the local defenses. Our objective was to establish whether treatment of the disease influences low salivary EGF concentrations. METHODS: The spontaneous whole saliva of 20 adults with LPR was sampled at a tertiary teaching hospital before and after a 16-week course of full-dose proton pump inhibitor and compared to that of 12 healthy controls. Salivary EGF concentrations were established with a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Although the mean salivary EGF concentrations were higher before treatment than after treatment and control of the disease (25,083 versus 19,359 pg/mL), this difference was not statistically significant (p = 0.065). The mean salivary EGF concentration of healthy control subjects was significantly higher (54,509 pg/mL; p < 0.0001). CONCLUSIONS: Both before and after treatment, patients with reflux laryngitis present lower salivary EGF concentrations than healthy control subjects, suggesting a primary deficit in their protective mechanisms.