Transcriptomic analysis identifies lactoferrin-induced quiescent circuits in neonatal macrophages

IntroductionUpon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derived macrophages.MethodsCord blood-derived monocytes were differentiated with M-CSF in presence or absence of 500 µg/mL hLF for 7 days and afterwards stimulated with 1 ng/mL LPS or left untreated. RNA was then isolated and subjected to microarray analysis.ResultsDifferentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, near-complete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples.DiscussionThe global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate the ontogenetical relevance of hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein’s potential therapeutic relevance

Cross-sectional survey and Bayesian network model analysis of traditional Chinese medicine in Austria: investigating public awareness, usage determinants and perception of scientific support

Objectives Despite the paucity of evidence verifying its efficacy and safety, traditional Chinese medicine (TCM) is expanding in popularity and political support. Decisions to include TCM diagnoses in the International Classification of Diseases 11th Revision and campaigns to integrate TCM into national healthcare systems have occurred while public perception and usage of TCM, especially in Europe, remains undetermined. Accordingly, this study investigates TCM’s popularity, usage and perceived scientific support, as well as its relationship to homeopathy and vaccinations.Design/Setting We performed a cross-sectional survey of the Austrian population. Participants were either recruited on the street (in-person) or online (web-link) via a popular Austrian newspaper.Participants 1382 individuals completed our survey. The sample was poststratified according to data derived from Austria’s Federal Statistical Office.Outcome measures Associations between sociodemographic factors, opinion towards TCM and usage of complementary medicine (CAM) were investigated using a Bayesian graphical model.Results Within our poststratified sample, TCM was broadly known (89.9% of women, 90.6% of men), with 58.9% of women and 39.5% of men using TCM between 2016 and 2019. Moreover, 66.4% of women and 49.7% of men agreed with TCM being supported by science. We found a positive relationship between perceived scientific support for TCM and trust in TCM-certified medical doctors (ρ=0.59, 95% CI 0.46 to 0.73). Moreover, perceived scientific support for TCM was negatively correlated with proclivity to get vaccinated (ρ=−0.26, 95% CI −0.43 to –0.08). Additionally, our network model yielded associations between TCM-related, homeopathy-related and vaccination-related variables.Conclusions TCM is widely known within the Austrian general population and used by a substantial proportion. However, a disparity exists between the commonly held public perception that TCM is scientific and findings from evidence-based studies. Emphasis should be placed on supporting the distribution of unbiased, science-driven information

Image_1_Transcriptomic analysis identifies lactoferrin-induced quiescent circuits in neonatal macrophages.jpeg

IntroductionUpon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derived macrophages.MethodsCord blood-derived monocytes were differentiated with M-CSF in presence or absence of 500 µg/mL hLF for 7 days and afterwards stimulated with 1 ng/mL LPS or left untreated. RNA was then isolated and subjected to microarray analysis.ResultsDifferentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, near-complete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples.DiscussionThe global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate the ontogenetical relevance of hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein’s potential therapeutic relevance.</p