Project description:We sought to elucidate the differentially expressed host factors in bronchoalveolar lavage cells (BALc) from nontuberculous mycobacteria (NTM)-infected subjects by studying the host transcriptome in during infection. A heatmap was created from the normalized expression of selected genes that showed statistically significant differential expression between NTM-infected and uninfected subjects. Genes with similar expression patterns were grouped and the most highly expressed genes are shown. One of the most differentially expressed gene in the NTM-infected group was the CFD (complement factor D) gene. Of note, a statistically significant three-fold increase in expression of the CAMP gene, encoding the LL-37 peptide was observed in the NTM-infected subject group (padj=0.05).
Project description:Background: Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Currently, there is no method to predict whether patients with cystic fibrosis will develop disease related to non-tuberculous mycobacteria. In non cystic fibrosis populations, several genetic susceptibility factors have been described. In this study, we examined whether patients with cystic fibrosis demonstrate a similar pattern of genetic susceptibility and explored host immune-related biomarkers predictive of NTM pulmonary disease (NTM-PD). Methods: We evaluated whole blood gene expression using bulk RNA-seq in a cohort of CF patients at the time of first isolation of NTM. Differential gene expression was compared in patients who did (n = 12) vs. did not (n= 30) develop NTM-PD following first NTM growth. Results: No differences in demographics or composition of white blood cell sample populations at the time of sample collection were identified between groups. There were no significant differences in the expression of genes previously reported to confer susceptibility to NTM-PD in non-CF populations. However, CF patients who went on to develop NTM-PD had higher expression of genes involved in the interferon ( and ), tumor necrosis factor, and IL6 STAT3 JAK pathways. Conclusion: Patients with CF who develop NTM-PD have increased expression of genes involved in innate immunity, in contrast to non-CF populations where these responses seem to be suppressed.
Project description:Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role.
Project description:These are sputum samples collected from 8 individuals with cystic fibrosis during the course of routine clinical care. They were initially stored at 4C for up to 24 hours then stored at -80C. No processing has been done to the sputum prior to freezing. For each individual there are sputum samples collected both before and after the individual had his or her first positive sputum culture for nontuberculous mycobacteria (NTM). The individuals experienced different clinical courses after their infection.
Project description:This series of mouse expression database represents samples contributed by researchers at University of Cincinnati and Cincinnati Children's Hospital profiles Keywords: other
