Differential expression of monocyte surface markers among TB patients with diabetes co-morbidity

Stew, Samuel S.; Martinez, Perla J.; Schlesinger, Larry S.; Restrepo, Blanca I.

doi:10.1016/s1472-9792(13)70015-5

Cited by 24 publications

(19 citation statements)

References 32 publications

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“…To determine whether DM also affects monocytes from TB patients, we compared the expression of monocyte surface markers from TB-DM and TB-no DM patients. 44 By multivariate analysis the monocytes from TB-DM had higher expression of CCR2, which coincides with the reported up-regulation of its ligand CCL2 (MCP-1) in sera from DM patients. 45 Future studies will determine whether this higher CCR2 expression may restrain the migration of diabetic monocytes from the blood to the site of Mtb infection in the lung, or within the lung and its regional lymph nodes as suggested in the mouse model of TB and DM.…”

Section: Impact Of Dm On the Natural History Of Tbsupporting

confidence: 77%

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Restrepo¹,

Schlesinger²

2013

Tuberculosis

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Tuberculosis (TB) is known to be fueled by HIV as well as social and economic factors. With progression of the diabetes mellitus (DM) pandemic in countries where TB is also endemic, focus is increasing on the potential links between DM and TB. Despite the magnitude of the DM-TB association woldwide, it is striking how little we know about the underlying biology that promotes this association which is a major concern to public health. In this review we summarize current findings regarding the alterations in the innate and adaptive immune responses of DM patients to Mycobacterium tuberculosis (Mtb). Current findings suggest underperforming innate immunity followed by a hyper-reactive cellular response to Mtb, but the contribution of these altered responses to TB susceptibility or to the more adverse clinical outcomes of TB patients with DM remains unclear. Elucidating the basic mechanisms underlying the higher susceptibility of DM patients to TB should lead to a strategy for stratification of the millions of DM patients worldwide into those with the highest TB risk for targeted TB prevention.

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Section: Impact Of Dm On the Natural History Of Tbsupporting

confidence: 77%

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Restrepo¹,

Schlesinger²

2013

Tuberculosis

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“…Activated inflammatory macrophages are closely linked to many diabetic complications through the generation of significant levels of pro‐inflammatory cytokines and ROS (Table ) . While inflammatory cytokine production by unstimulated macrophages is higher in individuals with diabetes, infection‐induced cytokine production tends to be impaired compared with non‐diabetic individuals . This may be associated with reduced macrophage migration to sites of infection as suggested by lower levels of CCL2 in lung lysates in experimental models of diabetes and tuberculosis .…”

Section: Effect Of Diabetes On the Early Immune Response To Intracellmentioning

confidence: 99%

“…While inflammatory cytokine production by unstimulated macrophages is higher in individuals with diabetes, infection‐induced cytokine production tends to be impaired compared with non‐diabetic individuals . This may be associated with reduced macrophage migration to sites of infection as suggested by lower levels of CCL2 in lung lysates in experimental models of diabetes and tuberculosis . In addition to impaired recruitment, clinical and experimental evidence indicates that monocytes from individuals with diabetes have reduced phagocytic and antibacterial activity against M. tuberculosis and B. pseudomallei in vitro .…”

Section: Effect Of Diabetes On the Early Immune Response To Intracellmentioning

confidence: 99%

Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections

et al. 2015

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SummaryDiabetes has been recognized as an important risk factor for a variety of intracellular bacterial infections, but research into the dysregulated immune mechanisms contributing to the impaired host-pathogen interactions is in its infancy. Diabetes is characterized by a chronic state of lowgrade inflammation due to activation of pro-inflammatory mediators and increased formation of advanced glycation end products. Increased oxidative stress also exacerbates the chronic inflammatory processes observed in diabetes. The reduced phagocytic and antibacterial activity of neutrophils and macrophages provides an intracellular niche for the pathogen to replicate. Phagocytic and antibacterial dysfunction may be mediated directly through altered glucose metabolism and oxidative stress. Furthermore, impaired activation of natural killer cells contributes to decreased levels of interferon-c, required for promoting macrophage antibacterial mechanisms. Together with impaired dendritic cell function, this impedes timely activation of adaptive immune responses. Increased intracellular oxidation of antigen-presenting cells in individuals with diabetes alters the cytokine profile generated and the subsequent balance of T-cell immunity. The establishment of acute intracellular bacterial infections in the diabetic host is associated with impaired T-cell-mediated immune responses. Concomitant to the greater intracellular bacterial burden and potential cumulative effect of chronic inflammatory processes, late hyper-inflammatory cytokine responses are often observed in individuals with diabetes, contributing to systemic pathology. The convergence of intracellular bacterial infections and diabetes poses new challenges for immunologists, providing the impetus for multidisciplinary research.

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“…These authors showed that post-trauma, two phases of release of RAGE ligands occurred and they speculated that their interaction with RAGE contributed to modulation of immune responses after severe injuries 57 . Evidence that the changes in RAGE expression in such settings is not spurious but, rather, that specific cues in distinct environments may result in alterations in monocyte RAGE expression was evident from studies by Stew and colleagues who showed that there no differences in monocyte cell surface RAGE expression between tuberculosis patients with or without type 2 diabetes 58 .…”

Section: Rage and Signal Transductionmentioning

confidence: 99%

2016 ATVB Plenary Lecture

Schmidt

2017

ATVB

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The receptor for advanced glycation endproducts (RAGE) interacts with a unique repertoire of ligands that form and collect in the tissues and circulation in diabetes, aging, inflammation, renal failure and obesity. RAGE is expressed on multiple cell types linked to tissue perturbation in these settings. This Brief Review focuses on the role of RAGE in monocytes/macrophages and how RAGE ligand engagement on these cells mediates seminal changes in monocyte/macrophage migration, oxidative stress, cholesterol efflux and pro- vs. anti-inflammatory cues that signal to tissue damage. Studies using mice devoid of Ager (gene encoding RAGE) or pharmacological antagonists of RAGE are protective in animal models of diabetes, atherosclerosis, and high fat diet-induced obesity, in least in part through key roles in monocytes/macrophages. RAGE signal transduction requires the interaction of RAGE cytoplasmic domain with the formin, DIAPH1 and novel antagonists of this interaction show significant promise in attenuation of the maladaptive effects of RAGE ligands in cellular and in vivo models. Finally, this Brief Review discusses evidence for RAGE axis perturbation in human monocytes/macrophages and how tracing RAGE activity in these cells may identify target engagement biomarkers of RAGE antagonism for future clinical trials.

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Differential expression of monocyte surface markers among TB patients with diabetes co-morbidity

Cited by 24 publications

References 32 publications

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections

2016 ATVB Plenary Lecture

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