Project description:Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. Objective: We hypothesized that children raised in farm environments have a lower incidence of viral illnesses over the first two years of life than non-farm children. We also analyzed between farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. Methods: The Wisconsin Infant Study Cohort (WISC) birth cohort enrolled farm and non-farm pregnant women from central Wisconsin. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression at age two years was compared to farm exposure and respiratory illness history. Results: There was a higher rate of respiratory illnesses in the non-farm vs. farm group (rate ratio 0.82 [0.69,0.97], p=0.020), but no significant differences in wheezing illnesses. There was a stepwise reduction in rates of respiratory illnesses in children exposed at least weekly to 0, 1, or ≥2 animals (p=0.006). In analyzing nasal cell gene expression, farm exposures and preceding respiratory illnesses were positively related to gene signatures for mononuclear cells and innate and antimicrobial responses. Conclusions: Children exposed to farms and farm animals had lower rates of respiratory illnesses over the first two years of life. Both farm exposures and preceding respiratory illnesses were associated with increased innate immune responses, suggesting that these exposures stimulate mucosal immune responses to reduce subsequent illness frequency.
Project description:Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations. Upon the onset of ‘common cold’, volunteers were instructed to attend the first of three required visits to the study clinic. The first and second visits were designed to obtain samples and clinical data during the early and late stages of symptomatic illness respectively, whereas the third visit would occur when volunteers were asymptomatic and serve as a prospective baseline (BL) for the study.
Project description:Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations.
Project description:Antigen uptake, processing, trafficking and presentation in nasal mucosal tissues are regulated by complex intra- and inter-cellular signalling events. Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction. We used microarrays to detail the global expression of genes in murine nasal mucosa underlying immune induction with a non-inflammatory nanoemulsion nasal adjuvant.
Project description:The aim of this study was to perform a genome-wide transcriptional analysis (mRNA + microRNA) during in vitro mucociliary differentiation of primary human basal stem/progenitors cells (BSCs) cultured at the air-liquid interface (ALI) system. We used microarrays to detail the global gene expression underlying mucociliary differentiation of human upper airways basal stem/progenitor cells isolated from nasal polyps and control nasal mucosa.
Project description:To evaluate the roles of DUOX2 in flagellin- induced inflammatory response in mouse nasal mucosa. Wild type (Duox2+/+) and Duox2 knockout (Duox2-/-) mice were stimulated with 1 M-NM-<g/ml of flagellin for 4h. 422 genes (> 2 fold) were up-regulated in nasal mucosa of Duox2+/+ that was treated with flagellin and the full list of genes is presented in Supplemental Table II. These genes included the following defense- and immune response-related genes : Cytokine/chemokine-related genes (CCL20, CCR2, CCR5, CXCL2, CXCL5, CXCL9, CXCL16, IL18RAP, TNFAIP2, IL1B EAR2, FPR1), Granulocyte-related genes (IL8RB, MPO, PRG2, PPBP, PRG3), interferon-related genes (IFITM6, IFI47), macrophage related genes (IL1B, S100A9), and T-cell mediated immune response related genes (H2-Q6, IL1F9). In addition, signal transduction (PPBP, OLFR60, P2RY10) and cell adhesion (SELL, SELP, ICAM1, DSG1A, DSG3, VCAM1) related genes were also increased by flagellin treatment. These genes were selected based on the biological processes and molecular functions of their gene ontology. However, the increase of inflammation and immune response related genes by flagellin treatment were diminished in the nasal mucosa of the Duox2-/- mice compared with that of Duox2+/+ mice. Wild type (Duox2+/+) and Duox2 knockout (Duox2-/-) mice received either PBS (control) or flagellin (5 ug/ml) intranasally for 4h.
Project description:Understanding on pathogenesis of COVID-19 is rapidly growing, but primary target cells of SARS-CoV-2 infection is still not known. Here, we performed single cell RNA sequencing on human nasal mucosa tissue to investigate the expression patterns of host cell entry factors of SARS-CoV-2.