Project description:The transcriptomic innate immune response derived from human nasal epithelial cells depends on how Streptococcus pneumoniae colonises the nasopharynx. This study compared three wild type strains and one deficient in pneumolysin to explore the pathways of epithelial activation following a three hour infection in vitro.
Project description:The ability of mucosal epithelia to sustain asymptomatic colonization by pathogens, such as Streptococcus pneumoniae (Spn), remains a significant and unresolved scientific question. This study reveals that mucins—the main gel-forming elements of mucus—and their associated glycans, suppress the expression of pneumolysin, a Spn toxin that causes tissue injury and triggers inflammatory responses. These findings highlight a unique protective function of mucins, offering insights into potential therapeutic strategies.
Project description:A two-hit model of adenoviral vector delivery of active transforming growth factor-β (TGFb) 1 to induce fibrosis in mice in conjunction with treatment of the mice with purified pneumolysin from Streptococcus pneumoniae was applied to characterize the role of this virulence factor on fibrosis perpetuation in mice The study was supported by a BMBF grant for the German Center for Lung Research, partner site BREATH (Biomedical Research in Endstage and Obstructive Lung Disease Hannover)
Project description:Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. The release of the pore-forming cholesterol-dependent cytolysin (CDC) pneumolysin (PLY) and hydrogen peroxide (H2O2), a physiological metabolite, is an important virulence determinant of pneumococci.
Project description:Analysis of the pulmonary gene expression in two mouse strains BALB/cOlaHsd (BALB/c) and CBA/CaOlaHsd (CBA/Ca) after infection with various serotypes of Streptococcus pneumoniae. BALB/c mice show high resistance to infection with S. pneumoniae strain D39 (serotype 2), while CBA/Ca mice are highly susceptible. The lung samples of BALB/c and CBA/Ca were collected at 6h post-infection with one of the tested pneumococcal serotypes (2, 3, 6B and 19F) and for control animals (PBS-treated). Additionally lung samples from both mouse strains were collected at 12h and 24h post-infection with pneumococcal strain D39. The lists of differentially expressed genes were created by the comparison of infected versus PBS-treated animals and infected BALB/c versus infected CBA/Ca for each pneumococcal strain. The tested hypotheses were: 1) infection with S. pneumoniae will change the pulmonary transcriptomes of both mouse strains 2) The pulmonary gene expression will be specific for mouse strains and for the pneumococcal serotype and 3) The change in the pulmonary gene expression will associate with future clinical outcome of infection or with the type of observed inflammatory responses. Total RNA obtained from lung tissue from BALB/cOlaHsd and CBA/CaOlaHsd mouse strains (Harlan) post intranasal infection with Streptococcus pneumoniae of various serotypes (2, 3, 6B and 19F) dose 5.0E06 CFU or PBS-treated animals
Project description:We used genome-wide transcriptional profiling by microarray to assess the contribution of pneumolysin on macrophage innate immune responses to the TIGR4 strain of Streptococcus pneumoniae (Spn). We focused on the early transcriptional responses at 4 hours after inoculation of human blood monocyte-derived macrophage cultures with Spn at a multiplicity of 10 bacteria to each cell. We compared transcriptomes in the presence and absence of wildtype or pneumolysin-deficient TIGR4 Spn, and also in the presence and absence of cytochalasin D to assess whether there is a differential effect of pneumolysin on innate immune responses with and without bacterial internalisation.
Project description:Analysis of pulmonary gene expression in two mouse strains, resistant (BALB/c) and susceptible (CBA/Ca) to Streptococcus pneumoniae infection. Data collected at 6h post-infection and for control animals (PBS-treated). The list of differentially expressed genes was created by comparisons of infected versus PBS-treated animals and PBS-treated BALB/c versus CBA/Ca. The hypothesis tested in the present study was that pulmonary transcriptomes of both mouse strains differ during pneumococcal infection and in non-disease conditions. Results provided important information on differences in immune responses between both mouse strains. The results identified genes and pathways uniquely regulated by only one of the tested mouse strains helping to understand molecular mechanism behind resistance or susceptibility to pneumococcal infections. Total RNA obtained from lung tissue from BALB/cOlaHsd and CBA/CaOlaHsd mouse strains (Harlan) 6 hours post intranasal infection with Streptococcus pneumoniae serotype 2 strain D39 dose 5.0E06 or PBS-treated animals
Project description:Zebrafish embryo has been emerging as an interesting model of infection due to their fecundity, transparency and availability of genetic tools. Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia, sepsis and meningitis. The bacteria expresses a very important virulence factor, pneumolysin able to form pores on cholesterol-based membranes and to activate innate immune system. Here, we exploited the recently described dual RNA-seq to simultaneously measure genome-wide expression of host and pathogen eight hours into infection. Functional enrichment analysis showed certain pathways such as autophagy and apoptosis being activated in the host while stress responses including pneumococcal competence. The study is the first to describe dual RNA-seq application in whole organism sequencing in infection model.
Project description:Analysis of the pulmonary gene expression in two mouse strains BALB/cOlaHsd (BALB/c) and CBA/CaOlaHsd (CBA/Ca) after infection with various serotypes of Streptococcus pneumoniae. BALB/c mice show high resistance to infection with S. pneumoniae strain D39 (serotype 2), while CBA/Ca mice are highly susceptible. The lung samples of BALB/c and CBA/Ca were collected at 6h post-infection with one of the tested pneumococcal serotypes (2, 3, 6B and 19F) and for control animals (PBS-treated). Additionally lung samples from both mouse strains were collected at 12h and 24h post-infection with pneumococcal strain D39. The lists of differentially expressed genes were created by the comparison of infected versus PBS-treated animals and infected BALB/c versus infected CBA/Ca for each pneumococcal strain. The tested hypotheses were: 1) infection with S. pneumoniae will change the pulmonary transcriptomes of both mouse strains 2) The pulmonary gene expression will be specific for mouse strains and for the pneumococcal serotype and 3) The change in the pulmonary gene expression will associate with future clinical outcome of infection or with the type of observed inflammatory responses.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.