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PAGES: DOI: 10.1590/0074-02760170326 Full paper
Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

Nallely Lopez-Lopez1,2, Ana Gabriela Ramos Martinez1,2, Mariana Haydee Garcia-Hernandez1, Rogelio Hernandez-Pando3, Julio Enrique Castañeda-Delgado4, Geanncarlo Lugo-Villarino5, Céline Cougoule5, Olivier Neyrolles5, Bruno Rivas-Santiago1, Monica Alejandra Valtierra-Alvarado1,2, Marisela Rubio-Caceres6, Jose Antonio Enciso-Moreno1, Carmen Judith Serrano1,+

1Instituto Mexicano del Seguro Social, Unidad de Investigación Biomédica Zacatecas, Zacatecas, Mexico
2Universidad Autónoma de San Luis Potosí, Escuela de Medicina, Departamento de Inmunología, San Luis Potosí, Mexico
3Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán, Departamento de Patología, Sección de Patología Experimental, Ciudad de México, México
4Consejo Nacional de Ciencia Y Tecnología-CONACyT, Cátedras CONACyT, Unidad de Investigación Biomédica Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, México
5Université Paul Sabatier, Centre National de la Recherche Scientifique, Institut de Pharmacologie et Biologie Structurale, Toulouse, France
6Instituto Mexicano del Seguro Social, Unidad de Medicina Familiar No. 4, Guadalupe, Zacatecas, México


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.

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Financial support: Fondo de Investigación en Salud from Instituto Mexicano del Seguro Social, México (grant no. FIS/IMSS/PROT/G14/1340).
NL-L, AGRM and MAVA were supported by ConaCyT [fellowship No. 371771 (PhD), 417995 (PhD), 705890 (MD), respectively].
NL-L and AGRM contributed equally to this work.
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Received 11 August 2017
Accepted 31 December 2017