Hyperglycemia and dyslipidemia: Reduced HLA-DR expression in monocyte subpopulations from diabetes patients

Restrepo, Blanca I.; Twahirwa, Marcel; Jagannath, Chinnaswamy

doi:10.1016/j.humimm.2020.11.005

Cited by 18 publications

(22 citation statements)

References 31 publications

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“…Our results showed that T2D modifies in MDM the basal expression levels of activation markers, such as HLA‐DR and CD86 (key molecules for antigen presentation), and the macrophage marker CD163 (inflammation regulator). These data are in line with previous results by our group and other authors in monocytes 18,19 and MDM 18 from T2D patients, and they are also consistent with the report in the human monocyte cell line THP‐1, where HLA‐DR and CD86 expression was inhibited in cells exposed to high glucose and palmitate concentrations 20 . Overall, these data suggest that T2D itself alters the expression of markers associated with specific functions, which would translate to immune dysfunction and susceptibility to pathogens.…”

Section: Discussionsupporting

confidence: 92%

“…These results are in accordance with different studies reporting that leukocytes from T2D patients, such as whole blood cells, 45 monocytes 46 and MDM, 18,45 showed similar Mtb‐antimicrobial activity when compared to controls without diabetes. In addition, MDM derived from TB patients showed a reduced capacity to kill Mtb that is not modified by the diabetes status (patients with the comorbidity TB‐T2D), 19 suggesting that permissivity of human monocytes and macrophages to Mtb growth is not exacerbated by T2D. Future studies shall address whether the high abundance of IL‐1β in MDM derived from cmMTB‐T2D exposure is actually responsible for the lack of the expected exacerbation of the Mtb intracellular burden.…”

Section: Discussionmentioning

confidence: 99%

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Impact of type 2 diabetes on the capacity of human macrophages infected with Mycobacterium tuberculosis to modulate monocyte differentiation through a bystander effect

et al. 2021

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Type 2 diabetes mellitus (T2D) is a risk factor for the development of tuberculosis (TB) through mechanisms poorly understood. Monocytes and macrophages are key effector cells to control TB, but they are also subverted by Mycobacterium tuberculosis (Mtb). Specifically, Mtb can induce a bystander effect that skews monocyte differentiation towards macrophages with a permissive phenotype to infection. Here, we evaluated whether T2D impacts this TB aspect. Our approach was to differentiate monocytes from healthy control (HC) subjects and T2D patients into macrophages (MDM), and then assess their response to Mtb infection, including their secretome content and bystander effect capacity. Through flow cytometric analyses, we found a lower level of activation markers in MDM from T2D patients than from HC in response to mock (HLA‐DR, CD86 and CD163) or Mtb challenge (CD14 and CD80). In spite of high TGF‐β1 levels in mock‐infected MDM from T2D patients, cytometric bead arrays indicated that there were no major differences in the secretome cytokine content in these cells relative to HC‐MDM, even in response to Mtb. Mimicking a bystander effect, the secretome of Mtb‐infected HC‐MDM drove HC monocytes towards MDM with a permissive phenotype for Mtb intracellular growth. However, the secretome from Mtb‐infected T2D‐MDM did not exacerbate the Mtb load compared to secretome from Mtb‐infected HC‐MDM, possibly due to the high IL‐1β production relative to Mtb‐infected HC‐MDM. Collectively, despite T2D affecting the basal MDM activation, our approach revealed that it has no major consequence on their response to Mtb or capacity to generate a bystander effect influencing monocyte differentiation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Impact of type 2 diabetes on the capacity of human macrophages infected with Mycobacterium tuberculosis to modulate monocyte differentiation through a bystander effect

et al. 2021

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“…Our findings raise the need to evaluate the occurrence of dysglycemia in old mice, and document its relationship to TB risk. Despite the lack of association between diabetes and TB in the elderly population, we recommend the screening for diabetes in all newly diagnosed elderly TB patients given that management of acute hyperglycemia is important for proper immune function against M. tuberculosis [40][41][42]. Furthermore, diabetes may be associated with adverse TB treatment outcomes in the elderly, as is the case for adults [5,43].…”

Section: Plos Onementioning

confidence: 99%

A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor

Scordo

Aguillón-Durán²,

Ayala³

et al. 2021

PLoS ONE

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Background Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. Methods Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (>60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. Results LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; p<0.001), but not in ReC (elderly 71.3% vs. adult 63.8%); p = 0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, type 2 diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). Conclusions We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population.

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“…Consistent with this, ex vivo phenotyping of human monocytes revealed that while triglycerides are associated with reduced HLA-DR cholesterols counterbalance this effect [53].…”

Section: Dyslipidemia and Tb Disease Severity: Cholesterol Vs Triglyceridesmentioning

confidence: 70%

“…In a subsequent study, the authors revealed that primary human monocytes from T2D patients had reduced expression of HLA-DR, a marker for antigen presentation. Interestingly, cholesterol levels including total cholesterol, HDL-or LDL-cholesterol were associated with higher HLA-DR expression [53]. These findings highlight that hyperglycemia cannot be studied in isolation without assessing the impact of dyslipidemia in susceptibility of T2D patients to TB.…”

Section: Contribution Of Hyperglycemia To Tb Disease Severity and Adverse Tb Treatment Outcomes 41 T2d-related Chronic Hyperglycemiamentioning

confidence: 90%

Diabetes-associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

Ngo

Bartlett

Ronacher

2021

Preprint

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Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

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Hyperglycemia and dyslipidemia: Reduced HLA-DR expression in monocyte subpopulations from diabetes patients

Cited by 18 publications

References 31 publications

Impact of type 2 diabetes on the capacity of human macrophages infected with Mycobacterium tuberculosis to modulate monocyte differentiation through a bystander effect

Impact of type 2 diabetes on the capacity of human macrophages infected with Mycobacterium tuberculosis to modulate monocyte differentiation through a bystander effect

A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor

Diabetes-associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

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