Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis
Mem. Inst. Oswaldo Cruz
; 113(4): e170326, 2018. tab, graf
Artigo
em Inglês
| LILACS
| ID: biblio-894912
Biblioteca responsável:
BR1.1
ABSTRACT
BACKGROUND Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated. FINDINGS The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1β, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes. CONCLUSIONS T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
Agenda de Saúde Sustentável para as Américas
/
ODS3 - Saúde e Bem-Estar
/
Doenças Negligenciadas
Problema de saúde:
Objetivo 9: Redução de doenças não transmissíveis
/
Objetivo 10: Doenças transmissíveis
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Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
/
Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis
/
Doenças Negligenciadas
/
Tuberculose
Base de dados:
LILACS
Assunto principal:
Contagem de Colônia Microbiana
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Fatores de risco
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2018
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
México
Instituição/País de afiliação:
Instituto Mexicano del Seguro Social/MX