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  • 1
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2024
    In:  Frontiers in Immunology Vol. 15 ( 2024-4-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 15 ( 2024-4-22)
    Abstract: Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2024.1392316
    DOI: 10.3389/fimmu.2024.1392316.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Online Resource
    〈b〉〈i〉Streptococcus pneumoniae〈/i〉〈/b〉 Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4〈sup〉+〈/sup〉 T Cells via Pneumolysin
    S. Karger AG ; 2022
    In:  Journal of Innate Immunity Vol. 14, No. 5 ( 2022), p. 569-580
    Details
    In: Journal of Innate Immunity, S. Karger AG, Vol. 14, No. 5 ( 2022), p. 569-580
    Abstract: Influenza A Virus (IAV), 〈 i 〉 Staphylococcus aureus 〈 /i 〉 (staphylococci), and 〈 i 〉 Streptococcus pneumoniae 〈 /i 〉 (pneumococci) are leading viral and bacterial causes of pneumonia. Dendritic cells (DCs) are present in the lower respiratory tract. They are characterized by low expression of co-stimulatory molecules, including CD80 and CD86 and high capacity of antigen uptake. Subsequently, DCs upregulate co-stimulatory signals and cytokine secretion to effectively induce T-cell priming. Here, we investigated these processes in response to bacterial and viral single as well as coinfections using human monocyte-derived (mo)DCs. Irrespective of single or coinfections, moDCs matured in response to IAV and/or staphylococcal infections, secreted a wide range of cytokines, and activated CD4 〈 sup 〉 + 〈 /sup 〉 , CD8 〈 sup 〉 + 〈 /sup 〉 as well as double-negative T cells. In contrast, pneumococcal single and coinfections impaired moDC maturation, which was characterized by low expression of CD80 and CD86, downregulated expression of CD40, and a mild cytokine release resulting in abrogated CD4 〈 sup 〉 + 〈 /sup 〉 T-cell activation. These actions were attributed to the cholesterol-dependent cytotoxin pneumolysin (Ply). Infections with a 〈 i 〉 ply 〈 /i 〉 -deficient mutant resulted in restored moDC maturation and exclusive CD4 〈 sup 〉 + 〈 /sup 〉 T-cell activation. These findings show that Ply has important immunomodulatory functions, supporting further investigations in specific modalities of Ply-DC interplay.
    Type of Medium: Online Resource
    ISSN: 1662-811X , 1662-8128
    URL: Article
    DOI: 10.1159/000522339
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2455818-7
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  • 3
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    Online Resource
    Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-10-18)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-10-18)
    Abstract: Seasonal Influenza A virus (IAV) infections can promote dissemination of upper respiratory tract commensals such as Streptococcus pneumoniae to the lower respiratory tract resulting in severe life-threatening pneumonia. Here, we aimed to compare innate immune responses in the lungs of healthy colonized and non-colonized mice after IAV challenge at the initial asymptomatic stage of infection. Responses during a severe bacterial pneumonia were profiled for comparison. Cytokine and innate immune cell imprints of the lungs were analyzed. Irrespective of the colonization status, mild H1N1 IAV infection was characterized by a bi-phasic disease progression resulting in full recovery of the animals. Already at the asymptomatic stage of viral infection, the pro-inflammatory cytokine response was as high as in pneumococcal pneumonia. Flow cytometry analyses revealed an early influx of inflammatory monocytes into the lungs. Neutrophil influx was mostly limited to bacterial infections. The majority of cells, except monocytes, displayed an activated phenotype characterized by elevated CCR2 and MHCII expression. In conclusion, we show that IAV challenge of colonized healthy mice does not automatically result in severe co-infection. However, a general local inflammatory response was noted at the asymptomatic stage of infection irrespective of the infection type.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-00211-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 4
    Online Resource
    Online Resource
    Cytokine Profiling in Influenza A Virus and Staphylococcal (Co-)Infections
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Infectious Microbes and Diseases Vol. 4, No. 4 ( 2022-12), p. 161-167
    Details
    In: Infectious Microbes and Diseases, Ovid Technologies (Wolters Kluwer Health), Vol. 4, No. 4 ( 2022-12), p. 161-167
    Abstract: Influenza A virus and Staphylococcus aureus are common causative agents of pneumonia. Co-infections with these two pathogens frequently occur and are characterized, among others, by higher morbidity and mortality due to hyper-inflammation of the lungs. Here, we aimed to profile systemic and local cytokine composition at early acute stages of pneumonia in a murine model. All mice recovered from single influenza A virus and/or staphylococcal infections. In contrast, co-infections led to a severe clinical outcome. While distinct cytokine patterns were detected in lungs of single-pathogen-infected animals, co-infections combined both virus- and bacteria-driven responses. However, analyses of infected human primary monocytic cells as well as bronchial epithelial cells did not reflect murine profiles. Based on infectious dose, mainly bacteria-driven responses were noted. The impact of single cells to cytokine composition of the lungs and translation of murine studies to humans remains uncertain and warrants further studies.
    Type of Medium: Online Resource
    ISSN: 2641-5917
    URL: Article
    DOI: 10.1097/IM9.0000000000000108
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 3099364-7
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