Impaired Recognition of<i>Mycobacterium tuberculosis</i>by Alveolar Macrophages From Diabetic Mice

Martínez, Núria; Ketheesan, Natkunam; West, Kim; Vallerskog, Therese; Kornfeld, Hardy

doi:10.1093/infdis/jiw436

Cited by 65 publications

(60 citation statements)

References 31 publications

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“…32 In mice, other phagocytic receptors, such as the macrophage receptor with collagenous structure (MARCO), are important for clearance of respiratory pathogens including Streptococcus pneumoniae and Mycobacterium tuberculosis. 35 In addition to phagocytosis, AMs secrete numerous cytokines and chemokines, including interleukin-6 (IL-6), tumour necrosis factor-a, monocyte chemoattractant protein 1, RANTES and granulocyte colony-stimulating factor, which recruit other inflammatory cells. 35 In addition to phagocytosis, AMs secrete numerous cytokines and chemokines, including interleukin-6 (IL-6), tumour necrosis factor-a, monocyte chemoattractant protein 1, RANTES and granulocyte colony-stimulating factor, which recruit other inflammatory cells.…”

Section: Alveolar Macrophagesmentioning

confidence: 99%

Tissue‐resident innate immunity in the lung

2019

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The lung is a unique organ that must protect against inhaled pathogens and toxins, without mounting a disproportionate response against harmless particulate matter and without compromising its vital function. Tissue-resident immune cells within the lung provide local immunity and protection from infection but are also responsible for causing disease when dysregulated. There is a growing appreciation of the importance of tissue-resident memory T cells to lung immunity, but non-recirculating, tissue-resident, innate immune cells also exist. These cells provide the first line of defence against pulmonary infection and are essential for co-ordinating the subsequent adaptive response. In this review, we discuss the main lung-resident innate immune subsets and their functions in common pulmonary diseases, such as influenza, bacterial pneumonia, asthma and inflammatory disorders.

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Section: Alveolar Macrophagesmentioning

confidence: 99%

Tissue‐resident innate immunity in the lung

2019

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“…Therefore, DM metabolite-induced increased ROS production may further contribute to the increased rate of relapse and death in TB patients with poor glycemic control. The diabetic phenotypes of alveolar macrophage recognition of M. tuberculosis and T cell hyper-responsiveness were also shown to be at least partially dependent on RAGE expression 57,24 . Thus, blocking the RAGE signaling pathway may reduce ROS generation and may prove useful in the context of TB-DM comorbidity.…”

Section: Ros As a Central Mediatormentioning

confidence: 99%

“…Given the higher prevalence of pulmonary (versus extrapulmonary) TB among DM patients,understanding this compartmentalization is particularly relevant 4,23 . Data from the mouse TB-DM model suggest that chronic hyperglycemia exerts unique effects on alveolar versus peritonal and bone marrow-derived macrophages 24 . Thus, integration of the observed immunometabolic abnormalities in pre-diabetic and diabetic hosts warrant futher investigation.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…The resulting delay in recruiting myeloid cells, including neutrophils and dendritic cells to the alveolar airspace, leads to a delay in transferring bacilli from the lung to the lymph node and a delay in priming the adaptive immune response 40 . Alveolar macrophages from diabetic mice have reduced CD14 and macrophage receptor with collagenous structure (MARCO) expression and display reduced phagocytosis 24 . Transfer of infected alveolar macrophages from diabetic mice into normoglycemic recipients confirmed an intrinsic defect that hinders T cell priming.…”

Section: Mouse Models To Study Tb-dm Comorbiditymentioning

confidence: 99%

“…The phenotype of diabetic alveolar macrophages is not shared by macrophages from other compartments in diabetic mice, such as the peritoneal or bone marrow-derived macrophages of chronic hyperglycemic mice. This unique macrophage phenotype appears to be dependent in part on the expression of RAGE 24 . Once the immune response to M. tuberculosis is initiated in the DM mice, it is excessive.…”

Section: Mouse Models To Study Tb-dm Comorbiditymentioning

confidence: 99%

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Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis and Diabetes

Ronacher

Crevel

Critchley

et al. 2017

Chest

Self Cite

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There is growing interest in the re-emerging interaction between type 2 diabetes (DM) and tuberculosis (TB), but the underlying biological mechanisms are poorly understood despite their possible implications in clinical management. Experts in epidemiological, public health, basic science and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-ocurrence of TB and DM. We identified gaps in current knowlege of altered immunity in DM patients during TB, where most studies suggest an under-performing innate immunity, but exaggerated adaptive immunity to Mycobacterium tuberculosis. Various molecular mechanisms and pathways that may underly these observations in the DM host. These include signaling induced by excess advanced glycation end products (AGE) and their receptor (RAGE), higher levels of reactive oxidative species and oxidative stress, epigenetic changes due to chronic hyperglycemia, altered nuclear receptors and/or differences in cell metabolism (immuno-metabolism). Studies in humans at different stages of DM (no DM, pre-DM and DM) or TB (latent or active TB) should be complemented with findings in animal models, which provide the unique opportunity to study early events in the host-pathogen interaction. Such studies could also help identify biomarkers that will complement clinical studies in order to tailor the prevention of TB-DM, or avoid the adverse TB treatment outcomes that are more likely in these patients. Such studies will also inform new approaches to host-directed therapies. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Summary box• Type 2 diabetes is a syndrome characterised by a range of metabolic (e.g. hyperglycemia, hyperlipidemia), inflammatory, vascular and other changes that may all contribute to increasing TB susceptibility and pathology.• Monocytes and macrophages from diabetic patients and mice have defects leading to altered interactions with M. tuberculosis and delayed adaptive immune responses.• Most human studies have been conducted in patients with active TB, where those with TB-DM comorbidity are characterised by increased secretion of Th1, Th17 and Th2 cytokines. However, the few studies in individuals at risk for TB (LTBI) suggest a different cytokine profile.• Molecular pathways that involve AGE/RAGE, ROS, nuclear receptors and cellular metabolism are potential targets for host-directed therapies to reduce TB susceptibility or pathology in DM patients.• Animal models for TB-DM can improve our understanding of underlying mechanisms and effective treatment approaches for the comorbidity of TB and DM. IntroductionType 2 diabetes mellitus (DM) increases the risk of many infectious diseases, including tuberculosis 1 (TB), and it is now recognized that the increasing DM prevalence in high TB incidence countries such as Sub-Saharan Africa (SSA) is a challenge to TB control. 2 The known association between a chronic syndome like DM and an infectious disease like TB requires the near term development...

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Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective

Ye,

Li,

Yang

et al. 2024

Exploration

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The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate.

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Impaired Recognition ofMycobacterium tuberculosisby Alveolar Macrophages From Diabetic Mice

Cited by 65 publications

References 31 publications

Tissue‐resident innate immunity in the lung

Tissue‐resident innate immunity in the lung

Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis and Diabetes

Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective

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