Diverse pathogen-associated molecular patterns affect transcription of genes in the toll-like receptor signaling pathway in goat blood.

Pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), peptidoglycan (PGN), Polyinosinic-polycytidylic acid (poly I:C), and CpG Oligodeoxynucleotides (ODN) are recognized by Toll-like receptors (TLR). This study aimed to investigate the effect of diverse PAMPs on the transcription of TLR signaling pathway genes in goat blood. Whole blood was collected from 3 female BoerXSpanish goats and treated with the following PAMPs: 10 µg/ml LPS, PGN, CpG ODN (2216), CpG ODN (2006), and 12.5 µg/ml Poly I:C. Blood-treated PBS served as a control. The expression of 84 genes in the human TLR signaling pathway RT2 PCR Array (Qiagen) was evaluated using real-time PCR. Treatment with PBS affected the expression of 74 genes, Poly I:C affected the expression of 40 genes, t ODN 2006 affected the expression of 50 genes, ODN 2216 affected the expression of 52 genes, LPS affected the expression of 49 genes, while PGN affected the expression of 49 genes. Our results show that PAMPs modulated and increased the expression of genes in the TLR signaling pathway. These results highlight important insights into how the host responds to different pathogens and may help design adjuvants for therapeutics and vaccines that target different.

The Effects of Race/Ethnicity, Age, and Area Deprivation Index (ADI) on COVID-19 Disease Early Dynamics: Washington, D.C. Case Study.

The COVID-19 pandemic and its associated mitigation strategies have significant psychosocial, behavioral, socioeconomic, and health impacts, particularly in vulnerable US populations. Different factors have been identified as influencers of the transmission rate; however, the effects of area deprivation index (as a measure of social determinants of health, SDoH) as a factor on COVID-19 disease early dynamics have not been established. We determined the effects of area deprivation index (ADI) and demographic factors on COVID-19 outcomes in Washington, D.C. This retrospective study used publicly available data on COVID-19 cases and mortality of Washington, D.C., during March 31st-July 4th, 2020. The main predictors included area deprivation index (ADI), age, and race/ethnicity. The ADI of each census block groups in D.C. (n=433) were obtained from Neighborhood Atlas map. Using a machine learning-based algorithm, the outcome variables were partitioned into time intervals: time duration (Pi, days), rate of change coefficient (Ei), and time segment load (Pi×Ei) for transmission rate and mortality. Correlation analysis and multiple linear regression models were used to determine associations between predictors and outcome variables. COVID-19 early transmission rate (E1) was highly correlated with ADI (SDoH; r= 0.88, p=0.0044) of the Washington, D.C. community. We also found positive association between ADI, age (0-17 years, r=0.91, p=0.0019), and race (African American/Black, r=0.86; p=0.0068) and COVID-19 outcomes. There was high variability in early transmission across the geographic regions (i.e., wards) of Washington, D.C., and this variability was driven by race/ethnic composition and ADI. Understanding the association of COVID-19 disease early transmission and mortality dynamics and key socio-demographic risk factors such as age, race, and ADI, as a measure of social determinants, will contribute to health equity/equality and distribution of economic resources/assistance and is essential for future predictive modeling of the COVID-19 pandemic to limit morbidity and mortality.

A Review of the Neutrophil Extracellular Traps (NETs) from Cow, Sheep and Goat Models.

This review provides insight into the importance of understanding NETosis in cows, sheep, and goats in light of the importance to their health, welfare and use as animal models. Neutrophils are essential to innate immunity, pathogen infection, and inflammatory diseases. The relevance of NETosis as a conserved innate immune response mechanism and the translational implications for public health are presented. Increased understanding of NETosis in ruminants will contribute to the prediction of pathologies and design of strategic interventions targeting NETs. This will help to control pathogens such as coronaviruses and inflammatory diseases such as mastitis that impact all mammals, including humans. Definition of unique attributes of NETosis in ruminants, in comparison to what has been observed in humans, has significant translational implications for one health and global food security, and thus warrants further study.

Cowpea polyphenol extract regulates galectin gene expression in bovine blood.

Galectins (GAL) are animal lectins that play important roles in the immune response through regulation of homeostasis and immune function. Bioactive polyphenols are able to bind and regulate galectins in inflammatory diseases. Cowpea is a nutritious and polyphenol-rich legume used as feed. The objective of the study was to evaluate the effect of cowpea polyphenol extract (CPE) on galectin gene transcription and translation in bovine peripheral blood. Blood from lactating cows (n = 10) were treated with CPE (10 µg/mL) or LPS (0.1 µg/mL), and control, to measure mRNA levels of bovine LGALS1, LGALS3, LGALS9, and some innate immune response genes. Secretion of GAL-1, GAL-3 and GAL-9 in plasma were measured using ELISAs. The mRNA expression of LGALS1, LGALS3 and LGALS9 decreased post CPE exposure. CPE decreased plasma GAL-1, but had no effect on GAL-3 and GAL-9. In addition, CPE decreased expression of TNFA, COX2 and upregulated TLR2, IL10 and IL4. LPS stimulation upregulated galectin genes expression and secretion. Overall, cowpea polyphenols modulated galectin expression, particularly GAL 1 in blood. The results provide a springboard for further studies on the use of polyphenol extracts from cowpea enriched feed supplements to target specific galectin genes for improved health and production in dairy cows.

Natural and synthetic pathogen associated molecular patterns modulate galectin expression in cow blood.

Pathogen-associated Molecular Patterns (PAMPs) are highly conserved structural motifs that are recognized by Pathogen Recognition receptors (PRRs) to initiate immune responses. Infection by these pathogens and the immune response to PAMPS such as lipopolysaccharide (LPS), Peptidoglycan (PGN), bacterial oligodeoxynucleotides [CpG oligodeoxynucleotides 2006 (CpG ODN2006) and CpG oligodeoxynucleotides 2216 (CpG ODN2216)], and viral RNA Polyinosinic-Polycytidylic Acid (Poly I:C), are associated with infectious and metabolic diseases in animals impacting health and production. It is established that PAMPs mediate the production of cytokines by binding to PRRs such as Toll-like receptors (TLR) on immune cells. Galectins (Gal) are carbohydrate-binding proteins that when expressed play essential roles in the resolution of infectious and metabolic diseases. Thus it is important to determine if the expression of galectin gene (LGALS) and Gal secretion in blood are affected by exposure to LPS and PGN, PolyI:C and bacterial CpG ODNs. LPS increased transcription of LGALS4 and 12 (2.5 and 2.02 folds respectively) and decreased secretion of Gal 4 (p < 0.05). PGN increased transcription of LGALS-1, -2, -3, -4, -7, and -12 (3.0, 2.3, 2.0, 4.1, 3.3, and 2.4 folds respectively) and secretion of Gal-8 and Gal-9 (p < 0.05). Poly I:C tended to increase the transcription of LGALS1, LGALS4, and LGALS8 (1.78, 1.88, and 1.73 folds respectively). Secretion of Gal-1, -3, -8 and nine were significantly increased in treated samples compared to control (p < 0.05). CpG ODN2006 did not cause any significant fold changes in LGALS transcription (FC < 2) but increased secretion of Gal-1, and-3 (p < 0.05) in plasma compared to control. Gal-4 was however reduced in plasma (p < 0.05). CpG ODN2216 increased transcription of LGALS1 and LGALS3 (3.8 and 1.6 folds respectively), but reduced LGALS2, LGALS4, LGALS7, and LGALS12 (-1.9, -2.0, -2.0 and; -2.7 folds respectively). Secretion of Gal-2 and -3 in plasma was increased compared to control (p < 0.05). Gal-4 secretion was reduced in plasma (p < 0.05). The results demonstrate that PAMPs differentially modulate galectin transcription and translation of galectins in cow blood.

Transcriptional profiling of the effect of lipopolysaccharide (LPS) pretreatment in blood from probiotics-treated dairy cows.

Probiotic supplements are beneficial for animal health and rumen function; and lipopolysaccharides (LPS) from gram negative bacteria have been associated with inflammatory diseases. In this study the transcriptional profile in whole blood collected from probiotics-treated cows was investigated in response to stimulation with lipopolysaccharides (LPS) in vitro. Microarray experiment was performed between LPS-treated and control samples using the Agilent one-color bovine v2 bovine (v2) 4x44K array slides. Global gene expression analysis identified 13,658 differentially expressed genes (fold change cutoff ≥ 2, P < 0.05), 3816 upregulated genes and 9842 downregulated genes in blood in response to LPS. Treatment with LPS resulted in increased expression of TLR4 (Fold change (FC) = 3.16) and transcription factor NFkB (FC = 5.4) and decreased the expression of genes including TLR1 (FC = - 2.54), TLR3 (FC = - 2.43), TLR10 (FC = - 3.88), NOD2 (FC = - 2.4), NOD1 (FC = - 2.45) and pro-inflammatory cytokine IL1B (- 3.27). The regulation of the genes involved in inflammation signaling pathway suggests that probiotics may stimulate the innate immune response of animal against parasitic and bacterial infections. We have provided a detailed description of the experimental design, microarray experiment and normalization and analysis of data which have been deposited into NCBI Gene Expression Omnibus (GEO): GSE75240.