5 research outputs found

    Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

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    Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two morphotypes with distinct effects on host cells and biological responses. The smooth (S) variant is recognized as the initial airway colonizer while the rough (R) is known to be a potent inflammatory inducer associated with invasive disease, but the underlying immunopathological mechanisms of the infection remain unsolved. We conducted a comparative stepwise dissection of the inflammatory response in S and R pathogenesis by monitoring infected transparent zebrafish embryos. Loss of TNFR1 function resulted in increased mortality with both variants, and was associated with unrestricted intramacrophage bacterial growth and decreased bactericidal activity. The use of transgenic zebrafish lines harboring fluorescent macrophages and neutrophils revealed that neutrophils, like macrophages, interact with M. abscessus at the initial infection sites. Impaired TNF signaling disrupted the IL8-dependent neutrophil mobilization, and the defect in neutrophil trafficking led to the formation of aberrant granulomas, extensive mycobacterial cording, unrestricted bacterial growth and subsequent larval death. Our findings emphasize the central role of neutrophils for the establishment and maintenance of the protective M. abscessus granulomas. These results also suggest that the TNF/IL8 inflammatory axis is necessary for protective immunity against M. abscessus and may be of clinical relevance to explain why immunosuppressive TNF therapy leads to the exacerbation of M. abscessus infections

    Enlivening a Community of Authentic Scholarship

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    Background: Critical and engaged qualitative scholarship depends on high-quality graduate training. The need to reexamine graduate student mentorship has become particularly pressing, given the high level of mental health distress experienced by students. It is unclear whether mentorship emerging within the student–advisor relationship is sufficient to ensure comprehensive mentorship. Innovative, experiential pedagogical approaches that integrate emotional and intellectual aspects are limited but may play a vital role in mentorship. There is a critical need to develop and study creative mentorship initiatives for emerging qualitative scholars. Methods: This study used interpretive description methodology and a community of practice theoretical framework to describe a faculty-mentored experience for graduate nursing students at the 2016 Qualitative Health Research Conference (FM-QHR) hosted by the International Institute for Qualitative Methodology. Participants completed written journals elucidating their experiences throughout FM-QHR. The textual data were analyzed using a constant comparative group analysis process, leading to the development of salient and interconnected themes. Results: Six graduate students and four faculty mentors submitted journals. Three interrelated themes articulate how this FM-QHR initiative enlivened a community of authentic scholarship: Questioning the Academic Self: Unvoiced Experiences of Angst, Uncertainty, and Fear ; Cocreating Authentic Community through Shared Vulnerability ; and Generative and Emergent Empowerment . Conclusion: These findings provide compelling insights into the importance of assisting students to navigate the emotional experiences that are a part of qualitative graduate training. Relational, mentorship initiatives hold potential to not only alleviate emotional distress but also support student empowerment, socialization, and entrance into a community of international qualitative researchers

    Animal cell cultures in microsporidial research: their general roles and their specific use for fish microsporidia

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