Anti-mycobacterial function of macrophages is impaired in a diet induced model of type 2 diabetes

Alim, Abdul; Sikder, Suchandan; Bridson, Tahnee; Rush, Catherine M.; Govan, Brenda; Ketheesan, Natkunam

doi:10.1016/j.tube.2016.12.002

Cited by 21 publications

(21 citation statements)

References 39 publications

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“…However, the MDMs derived from patients with T2D were unresponsive towards all Mtb strains. This is in line with a recent report describing the deficient production of TNF-α, IL-6, and MCP-1 in response to different Mycobacterium species by MFs isolated from mice with diabetes ( Alim et al 2017) . Moreover, the marked reduction in the production of IL-10 may be of consequence, because this cytokine plays a protective role in T2D and in the prevention of immunopathology induced by TB.…”

Section: Discussionsupporting

confidence: 93%

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

López-López

Martinez

García-Hernández

et al. 2018

Mem. Inst. Oswaldo Cruz

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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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Section: Discussionsupporting

confidence: 93%

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

López-López

Martinez

García-Hernández

et al. 2018

Mem. Inst. Oswaldo Cruz

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“…We found reduced expression of the M1 macrophage-associated cytokines Tnfa, Il6, and Il12b in the lungs of diabetic mice infected with MERS-CoV. This response is similar to what is observed after bacterial infection in which macrophages from diabetic mice or humans have been shown to have reduced phagocytic function and expression of TNF-α, IL-6, CCL2, and IL-12 (65)(66)(67). As proinflammatory gene expression was beginning to decline around 7 to 10 days after MERS-CoV infection, control mice upregulated the M2 marker Arg1, suggesting a switch to a more regulatory macrophage phenotype, which is important for resolving inflammation and promoting wound healing.…”

Section: Discussionsupporting

confidence: 84%

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

Kulcsar¹,

Coleman²,

Beck³

et al. 2019

JCI Insight

332

331

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“…Alveolar macrophages from diabetic mice had diminished expression of CD14 and also displayed reduced phagocytosis of M. tuberculosis . Similarly, in a diet‐induced model of type 2 DM, the authors observed that macrophages from diabetic mice exhibited reduced phagocytosis of mycolic‐acid‐coated beads, reduced internalization and killing of mycobacteria and altered cytokine responses …”

Section: Immunological Mechanisms Of Susceptibility In Animal Modelsmentioning

confidence: 88%

Influence of diabetes mellitus on immunity to human tuberculosis

2017

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SummaryType 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease.

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Anti-mycobacterial function of macrophages is impaired in a diet induced model of type 2 diabetes

Cited by 21 publications

References 39 publications

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis

Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection

Influence of diabetes mellitus on immunity to human tuberculosis

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