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
Article
in English
| LILACS
| ID: biblio-894912
Responsible library:
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.
Full text:
Available
Collection:
International databases
Health context:
Sustainable Health Agenda for the Americas
/
SDG3 - Health and Well-Being
/
Neglected Diseases
Health problem:
Goal 9: Noncommunicable diseases and mental health
/
Goal 10: Communicable diseases
/
Target 3.3: End transmission of communicable diseases
/
Target 3.4: Reduce premature mortality due to noncommunicable diseases
/
Neglected Diseases
/
Tuberculosis
Database:
LILACS
Main subject:
Colony Count, Microbial
/
Diabetes Mellitus, Type 2
Type of study:
Risk factors
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2018
Document type:
Article
/
Project document
Affiliation country:
Mexico
Institution/Affiliation country:
Instituto Mexicano del Seguro Social/MX