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dc.contributor.author
Fernández, Rocío del Valle
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Díaz, Ariana
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Bongiovanni, Bettina
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Gallucci, Georgina Florencia
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Bértola, Diego
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Gardeñez, Walter
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Lioi, Susana
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Bertolin, Yésica
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Galliano, Romina
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Bay, Maria Luisa
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Bottasso, Oscar Adelmo
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D'attilio, Luciano David
dc.date.available
2021-11-02T10:55:33Z
dc.date.issued
2020-03
dc.identifier.citation
Fernández, Rocío del Valle; Díaz, Ariana; Bongiovanni, Bettina; Gallucci, Georgina Florencia; Bértola, Diego; et al.; Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity; Frontiers Media; Frontiers in Endocrinology; 11; 3-2020; 1-16
dc.identifier.issn
1664-2392
dc.identifier.uri
http://hdl.handle.net/11336/145676
dc.description.abstract
Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem worldwide, further aggravated by the convergence of type 2 diabetes mellitus (DM) which constitutes an important risk factor for TB development. The worse scenario of patients with PTB and DM may be partly related to a more unbalanced defensive response. As such, newly diagnosed PTB patients with DM (TB+DM, n = 11) or not (TB, n = 21), as well as DM (n = 18) patients and pair matched controls (Co, n = 22), were investigated for the circulating immuno-endocrine-metabolic profile (ELISA), along with studies in peripheral blood mononuclear cells (PBMC) analyzing transcript expression (RT-qPCR) of mediators involved in glucocorticoid functionality. Given the hyperglycemic/hypercortisolemic scenario of TB+DM patients, PBMC were also exposed to stress-related cortisol concentrations (0.1 and 1 μM) and supraphysiologic glucose doses (10, 20, and 40 mM) and assessed for the specific response against Mtb stimulation (lymphoproliferation, -thymidine incorporation-, and cytokine production -bead-cytometry). All TB patients displayed increased plasma amounts of cortisol, growth hormone -hGH-, and proinflammatory mediators. In turn, TB+DM showed even higher levels of interferon gamma -IFN-γ- and hGH (vs. TB), or IL-6, C reactive protein, cortisol and hGH (vs. DM). Both DM groups had equally augmented values of IL-10. All TB patients showed decreased dehydroepiandrosterone- sulfate concentrations, even more in TB+DM cases. Leptin was also decreased in both TB cases, particularly in the TB group, revealing a lower body mass index, as well. Unlike PBMC from TB cases showing a decreased relationship between the glucocorticoids receptor (GR) isoforms (GRα/GRβ; functional isoform/negative isoform), cells from TB+DM patients had no changes in this regard, along with an increased expression of 11-beta hydroxysteroid dehydrogenase type-1, the enzyme facilitating intracellular cortisone to cortisol conversion. TB+DM patients also showed an increased Mtb antigen-driven lymphoproliferation. Compared to TB, DM and HCo counterparts, PBMC from TB+DM patients had a biased Th1 response to Mtb stimulation (increased IL-2 and IFN-γ production), even when exposed to inhibitory cortisol doses. TB+DM patients show a more unbalanced immuno-endocrine relationship, respect the non-diabetic counterparts, with a relative deficiency of cortisol immunomodulatory influences, despite their more favorable microenvironment for cortisol-mediated immune effects.
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application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CORTISOL
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DIABETES MELLITUS TYPE 2
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GLUCOSE
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IMMUNE-ENDOCRINE ALTERATIONS
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PULMONARY TUBERCULOSIS
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-04-28T20:42:41Z
dc.journal.volume
11
dc.journal.pagination
1-16
dc.journal.pais
Suiza
dc.journal.ciudad
Lausanne
dc.description.fil
Fil: Fernández, Rocío del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
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Fil: Díaz, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: Gallucci, Georgina Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
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Fil: Bértola, Diego. Universidad Nacional de Rosario; Argentina
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Fil: Gardeñez, Walter. Universidad Nacional de Rosario; Argentina
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Fil: Lioi, Susana. Hospital Provincial del Centenario; Argentina
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Fil: Bertolin, Yésica. Hospital Provincial del Centenario; Argentina
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Fil: Galliano, Romina. Hospital Provincial del Centenario; Argentina
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Fil: Bay, Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.journal.title
Frontiers in Endocrinology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fendo.2020.00126/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fendo.2020.00126
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