Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis
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) infec...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2018-02-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000400304&lng=en&tlng=en |
| _version_ | 1827844798779752448 |
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| author | Nallely Lopez-Lopez Ana Gabriela Ramos Martinez Mariana Haydee Garcia-Hernandez Rogelio Hernandez-Pando Julio Enrique Castañeda-Delgado Geanncarlo Lugo-Villarino Céline Cougoule Olivier Neyrolles Bruno Rivas-Santiago Monica Alejandra Valtierra-Alvarado Marisela Rubio-Caceres Jose Antonio Enciso-Moreno Carmen Judith Serrano |
| author_facet | Nallely Lopez-Lopez Ana Gabriela Ramos Martinez Mariana Haydee Garcia-Hernandez Rogelio Hernandez-Pando Julio Enrique Castañeda-Delgado Geanncarlo Lugo-Villarino Céline Cougoule Olivier Neyrolles Bruno Rivas-Santiago Monica Alejandra Valtierra-Alvarado Marisela Rubio-Caceres Jose Antonio Enciso-Moreno Carmen Judith Serrano |
| author_sort | Nallely Lopez-Lopez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T08:48:04Z |
| format | Article |
| id | doaj.art-b0f4238107ad41259cd69d79a7543132 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T08:48:04Z |
| publishDate | 2018-02-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-b0f4238107ad41259cd69d79a75431322023-09-02T16:25:25ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602018-02-01113410.1590/0074-02760170326S0074-02762018000400304Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosisNallely Lopez-LopezAna Gabriela Ramos MartinezMariana Haydee Garcia-HernandezRogelio Hernandez-PandoJulio Enrique Castañeda-DelgadoGeanncarlo Lugo-VillarinoCéline CougouleOlivier NeyrollesBruno Rivas-SantiagoMonica Alejandra Valtierra-AlvaradoMarisela Rubio-CaceresJose Antonio Enciso-MorenoCarmen Judith SerranoBACKGROUND 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000400304&lng=en&tlng=endiabetestuberculosisvirulencemacrophages |
| spellingShingle | Nallely Lopez-Lopez Ana Gabriela Ramos Martinez Mariana Haydee Garcia-Hernandez Rogelio Hernandez-Pando Julio Enrique Castañeda-Delgado Geanncarlo Lugo-Villarino Céline Cougoule Olivier Neyrolles Bruno Rivas-Santiago Monica Alejandra Valtierra-Alvarado Marisela Rubio-Caceres Jose Antonio Enciso-Moreno Carmen Judith Serrano Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis Memorias do Instituto Oswaldo Cruz diabetes tuberculosis virulence macrophages |
| title | Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis |
| title_full | Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis |
| title_fullStr | Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis |
| title_full_unstemmed | Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis |
| title_short | Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis |
| title_sort | type 2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond internalise and control mycobacterium tuberculosis |
| topic | diabetes tuberculosis virulence macrophages |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762018000400304&lng=en&tlng=en |
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