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1731. Immune Dysregulation in Mucormycosis

BACKGROUND: Mucormycosis is a fatal fungal infection with unique predisposition to infect diabetics. Dysregulated adaptive immunity contributes to the pathogenesis in all fungal diseases, but activated Th17 cells have laid a new dimension to chronic inflammatory response which was previously attribu...

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Detalles Bibliográficos
Autores principales: Gupta, Chhavi, Das, Shukla, Rai, Gargi, Singh, Praveen K, Dar, Sajad, Ansari, Mohammad A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808671/
http://dx.doi.org/10.1093/ofid/ofz360.1594
Descripción
Sumario:BACKGROUND: Mucormycosis is a fatal fungal infection with unique predisposition to infect diabetics. Dysregulated adaptive immunity contributes to the pathogenesis in all fungal diseases, but activated Th17 cells have laid a new dimension to chronic inflammatory response which was previously attributed to uncontrolled Th1 response. We attempted to study the Th17 and T regulatory (Treg) immune response in diabetic patients with mucormycosis and compared the data with a healthy control and a T2DM case without fungal infection. In addition we could follow-up one patient post 6-month treatment and performed immunological studies. METHODS: 2 mL of blood samples were collected in EDTA vial from two patients who were suffering from diabetes with mucormycosis for immunological investigations. Samples were also taken from age-matched T2DM patient without fungal infection and a healthy volunteer as controls for T-cell parameters. Repeat blood sample was taken to study immune parameters in one patient who was followed up after 6 months. The expression of various T-cell markers was analyzed by immunostaining with the antibodies against CD3, CD4, CD25, CD161, IL-23R [Becton Dickinson (BD) PharMingen]. Fluorescence profiles were analyzed using Flow Jo software (BD Biosciences). The results are expressed as a percentage of positive cells. RESULTS: The percentages of CD4+ cells were low in both patients when compared with and healthy control but it is much higher in diabetes case when compared with others. CD161+ cell population was higher in both patients when compared with healthy control and diabetic patient without fungal infection. The percentage of IL23R+ cells was significantly high in patient before treatment when compared with, healthy control and diabetics. and decline after treatment. The percentage positivity of CD25+ cells was highest in healthy control when compared with others. The profile of CD25+ cells was comparatively similar in patient before treatment and diabetics but we found a higher percentage, in patients after treatment. CONCLUSION: The findings in this study imminently indicate the mechanism of immune dysregulation involving Th17 and Treg pathways in mucormycosis and provide evidence that restoration of Th17/Treg may be considered as a therapeutic option for long-term benefit in diabetics. DISCLOSURES: All authors: No reported disclosures.