TREM-2: friend or foe in infectious diseases?

Matos, Amanda de Oliveira; Dantas, Pedro Henrique Dos Santos; Queiroz, Helena Auler Galvão de Barros; Silva‐Sales, Marcelle; Sales‐Campos, Helioswilton

doi:10.1080/1040841x.2022.2146481

Cited by 3 publications

(3 citation statements)

References 131 publications

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“…For macrophages in lungs and lymphoid organs (but not gut), we found a reduction of the APOE-TREM2 axis with age. TREM2 can have different effects on macrophage function, depending on context; it has been associated with induction of anti-inflammatory M2 function during infection, but can also promote phagocytosis and sustained inflammation in other infectious conditions 64,65 . Notably, TREM2 expression in microglia has been widely associated with age-driven dementia in Alzheimer's disease, and more recently, TREM2-macrophages have been associated with immunosuppression and lack of responses to immunotherapy in tumors 66 .…”

Section: Discussionmentioning

confidence: 99%

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

Wells,

Rainbow,

Mark

et al. 2024

Preprint

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The immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.

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Section: Discussionmentioning

confidence: 99%

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

Wells,

Rainbow,

Mark

et al. 2024

Preprint

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“…TREM-2 and TREM-1 were initially identified as innate myeloid cell receptors. A recent study reported that TREM-2 is expressed in several cell types, including macrophages, microglia, granulocytes, lymphocytes, dendritic cells and endothelial cells [ 38 ]. In this study, TREM-1 and TREM-2 were widely expressed on monocytes but were partially and selectively expressed on human T cells and B cells, which was consistent with a previous study [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

TREM-1, TREM-2 and their association with disease severity in patients with COVID-19

Fan,

Cheng,

Huang

et al. 2023

Annals of Medicine

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Background Delayed diagnosis and inadequate treatment caused by limited biomarkers are associated with the outcomes of COVID-19 patients. It is necessary to identify other promising biomarkers and candidate targets for defining dysregulated inflammatory states. Methods The triggering receptors expressed on myeloid cell (TREM)-1 and TREM-2 expression from hospitalized COVID-19 patients were characterized using ELISA and flow cytometry, respectively. Their correlation with disease severity and contrast with the main clinical indicators were evaluated. Results Increased expression of soluble TREM-1 and TREM-2 in the plasma of COVID-19 patients was found compared to the control group. Moreover, membrane-bound TREM-1 and TREM-2 expression was upregulated on the cell surface of circulating blood T cells from COVID-19 patients. Correlation analysis showed that sTREM-2 levels were negatively correlated with PaO 2 /FiO 2 , but positively correlated with C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels. Receiver operating characteristic curve analysis indicated that the predictive efficacy of sTREM-1 and sTREM-2 was equivalent to CRP and IL-6, and a little better than absolute leukocyte or neutrophil count and PCT in distinguishing disease severity. Conclusion TREM-2 and TREM-1 are critical host immune factors that response to SARS-COV-2 infection and could serve as potential diagnostic biomarkers and therapeutic targets for COVID-19.

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“…Furthermore, research has identi ed that TREM2 + macrophages can phagocytose and clear damaged cells in the liver, thereby suppressing chronic liver in ammation and non-alcoholic fatty liver disease induced by obesity [19]. Initially considered an antiin ammatory molecule during infections, recent research suggests that TREM2 can promote cellular phagocytosis of bacteria and enhance in ammatory responses [20]. The phagocytic activity dependent on TREM2 necessitates the presence of the full-length TREM2 protein [21].…”

Section: Introductionmentioning

confidence: 99%

TREM2 Recognition of Candidalysin Orchestrates Mucosal Immunity in Oropharyngeal Candidiasis

Deng,

Chen,

Liu

et al. 2024

Preprint

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The landscape of oral mucosal immunity, particularly in the context of oropharyngeal candidiasis (OPC), remains largely uncharted. By employing single-cell RNA sequencing (scRNA-seq) on murine models of OPC, we have illuminated the immune dynamics within this niche. We discovered a new subpopulation: TREM2-expressing macrophages, intrinsic to the oral mucosa, which infiltrated in response to Candida albicans (C. albicans) infection. However, these macrophages were significantly depleted under cortisone acetate (CA)-induced immunosuppression. This study unveiled the pattern recognition receptor (PRR) characteristics of TREM2 during OPC, where TREM2 demonstrated the ability to directly recognize candidalysin at positions G65, N73, and N91-K92, inducing downstream inflammatory signaling regulation of TNF-α, which orchestrated macrophage and neutrophil responses and influenced Th17 cell differentiation. As a result, the absence of TREM2 increases the susceptibility of mice to OPC. Conversely, administering TREM2 agonists has been shown to facilitate the clearance of OPC induced by CA in mice. Therefore, our findings expand the understanding of TREM2 beyond its known association with neurodegenerative diseases and metabolic disorders, positioning it as a key receptor in bridging the host-fungus immune interface, and providing novel therapeutic insights for glucocorticoid-induced OPC.

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TREM-2: friend or foe in infectious diseases?

Cited by 3 publications

References 131 publications

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

TREM-1, TREM-2 and their association with disease severity in patients with COVID-19

TREM2 Recognition of Candidalysin Orchestrates Mucosal Immunity in Oropharyngeal Candidiasis

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