Search

Background: Cystic fibrosis (CF) airways disease varies widely among patients with identical cystic fibrosis transmembrane conductance regulator (CFTR) genotypes. Robust airway inflammation is thought to be deleterious in CF; inter-individual variation in Toll-like receptor (TLR)-mediated innate immune inflammatory responses (TMIIR) might account for a portion of the phenotypic variation. We tested if TMIIR in people with CF are different than those of healthy controls, and whether higher TMIIR in people with CF are associated with reduced lung function., Methods: We cultured whole blood from clinically stable subjects with CF (n = 76) and healthy controls (n = 45) with TLR agonists, and measured cytokine production and expression of TLR-associated genes. We tested for differences in TLR-stimulated cytokine levels between subjects with CF and healthy subjects, and for associations between cytokine and gene expression levels with baseline lung function (forced expiratory volume in one second percent predicted (FEV 1 %)) and decline in FEV 1 % over time., Results: TMIIR in blood from subjects with CF were lower than in healthy controls. Expression of TLR regulators SARM1, TOLLIP, and AKT1 were downregulated in CF. In subjects with CF we found that lower TLR4-agonist-induced IL-8 was associated with lower FEV 1 % at enrollment (p<0.001) and with greater five year FEV 1 % decline (p<0.001)., Conclusions: TMIIR were lower in people with CF relative to healthy controls; however, unexpectedly, greater whole blood TMIIR were positively associated with lung function in people with CF. These findings suggest a complex interaction between inflammation and disease in people with CF., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2019. Published by Elsevier B.V.)

Based upon age and type of farming exposures, a wide range of studies demonstrate either protective or deleterious effects of the farming environment on asthma. In this review, we highlight key studies supporting the concept that farming exposure protects children from asthma and atopy based on studies performed largely in European pediatric cohorts. Various types of farming in certain regions appear to have a greater effect on asthma protection, as does the consumption of unpasteurized milk. In the United State, where concentrated animal feeding operations (CAFOs) are more common, asthma is increased in children exposed especially to swine CAFOs; whereas, rates of atopy and allergy are lower in these children. We also review studies evaluating the role of farming exposures both as a child and/or as an adult on asthma seen in adults. The importance of microbes in farming environments and the contribution of various components of the innate immune system including toll-like receptors to the underlying mechanisms of asthma related to farming exposures are also reviewed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Toxoplasma gondii has a highly clonal genetic structure classified into three major genetic types, I, II, and III, plus additional recombinant and atypical strains. In humans, type I and atypical strains usually associate with severe toxoplasmosis. Type II strains, predominantly identified in European countries and the United States, correlate with a differential course of toxoplasmosis. During pregnancy, the important protective role of the placenta against maternal-fetal T. gondii transmission has been reported. T. gondii preferentially colonizes extravillous trophoblasts as compared to syncytiotrophoblasts. The latter compartment was suggested to act as the real barrier to the fetal dissemination of T. gondii. Alterations in immune response to particular T. gondii strains were observed. Higher transcription levels of IP-10, IL-1β, IL-6, IL-10, IL-12 cytokines, and NF-κB translocation to the nucleus were more often documented for type II strains than type I strains. Since the induction of IL-12 during type II infection was Myd88-dependent, the involvement of Toll-like receptors (TLRs) in the immunity against these strains was suggested. Differential expression of TLRs depends on placental cell types and gestational age. The expression of TLR2 and TLR4 in the first trimester of pregnancy was reported only for villous cytotrophoblasts and extravillous trophoblasts, but not for syncytiotrophoblasts. The involvement of single-nucleotide polymorphisms (SNPs) in the TLR genes in infectious pathogenicity, including toxoplasmic retinochoroiditis, points at a possible involvement of TLR alterations in immunity against T. gondii. We conclude that studies on TLR contributions in the maternal-fetal transmission of particular parasite strains and congenital toxoplasmosis are warranted.