CLEC4E (Mincle) genetic variation associates with pulmonary tuberculosis in Guinea-Bissau (West Africa)

Olvany, Jasmine M.; Sausville, Lindsay N.; White, Marquitta J.; Tacconelli, Alessandra; Tavera, Gloria; Sobota, Rafal S.; Ciccacci, Cinzia; Bohlbro, Anders Solitander; Wejse, Christian; Williams, Scott M.; Sirugo, Giorgio

doi:10.1016/j.meegid.2020.104560

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…NFκB-related inflammatory cytokines were also produced through endogenous "inducible" Mincle, presumably because these pathways do not require kinetics-sensitive Ca 2+ signaling. These characteristics may optimize Mincle's critical function in infectious immunity in mice and humans (41)(42)(43). In contrast, gene sets specifically induced by Dectin-2 include several acquired immunityrelated genes, such as Il2.…”

Section: Discussionmentioning

confidence: 99%

The kinetics of signaling through the common FcRγ chain determine cytokine profiles in dendritic cells

2023

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The common Fc receptor γ (FcRγ) chain is a signaling subunit common to several immune receptors, but cellular responses induced by FcRγ-coupled receptors are diverse. We investigated the mechanisms by which FcRγ generates divergent signals when coupled to Dectin-2 and Mincle, structurally similar C-type lectin receptors that induce the release of different cytokines from dendritic cells. Chronological tracing of transcriptomic and epigenetic changes upon stimulation revealed that Dectin-2 induced early and strong signaling, whereas Mincle-mediated signaling was delayed, which reflects their expression patterns. Generation of early and strong FcRγ-Syk signaling by engineered chimeric receptors was sufficient to recapitulate a Dectin-2–like gene expression profile. Early Syk signaling selectively stimulated the activity of the calcium ion–activated transcription factor NFAT, which rapidly altered the chromatin status and transcription of the Il2 gene. In contrast, proinflammatory cytokines, such as TNF, were induced regardless of FcRγ signaling kinetics. These results suggest that the strength and timing of FcRγ-Syk signaling can alter the quality of cellular responses through kinetics-sensing signaling machineries.

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Section: Discussionmentioning

confidence: 99%

The kinetics of signaling through the common FcRγ chain determine cytokine profiles in dendritic cells

2023

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“…The emphasis on cell membrane-bound receptors, such as mannose receptor (M.R., CD206), dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), and Toll-Like Receptors (TLRs), provides a foundation for understanding the initial steps of host-pathogen recognition. [30][31][32] The selective focus on DC-SIGN and TLRs, particularly TLR2, TLR4, and TLR9, is well-justified, considering their extensive associations with TB susceptibility in the African population. 31,33,34 These receptors, expressed on various immune cells, serve as critical mediators in the immune response against Mycobacterium tuberculosis.…”

Section: Pathogen Recognition Receptors (Prrs)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Immune Genes and Their Association with Tuberculosis Susceptibility: An Analysis of the African Population

Wodelo,

Wampande,

Andama

et al. 2024

TACG

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Tuberculosis remains a global health concern, with substantial mortality rates worldwide. Genetic factors play a significant role in influencing susceptibility to tuberculosis. This review examines the current progress in studying polymorphisms within immune genes associated with tuberculosis susceptibility, focusing on African populations. The roles of various proteins, including Toll-like receptors, Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Non-Integrin, vitamin D nuclear receptor, soluble C-type lectins such as surfactant proteins A and D, C-type Lectin Domain Family 4 Member E, and mannose-binding lectin, phagocyte cytokines such as Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12, and Interleukin-18, and chemokines such as Interleukin-8, monocyte chemoattractant protein 1, Regulated upon activation, normal T-cell expressed and secreted are explored in the context of tuberculosis susceptibility. We also address the potential impact of genetic variants on protein functions, as well as how these findings align with the genetic polymorphisms not associated with tuberculosis. Functional studies in model systems provide insights into the intricate host-pathogen interactions and susceptibility mechanisms. Despite progress, gaps in knowledge remain, highlighting the need for further investigations. This review emphasizes the association of Single Nucleotide Polymorphisms with diverse aspects of tuberculosis pathogenesis, including disease detection and Mycobacterium tuberculosis infection.

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“…Mutations in NOD2, an intracellular PRR that recognizes TB, were also identified and associated with increased susceptibility [ 180 ]. Studies on another PRR, Mincle or CLEC4E, have also been conducted and the results suggest the influence of ethnicity on the presence of significant polymorphisms in this receptor [ 181 , 196 ]. SNPs in MARCO and CD36, two scavenger receptors, have been found related to pulmonary TB risk [ 182 ].…”

Section: Host Genetic Factorsmentioning

confidence: 99%

Resistance and Susceptibility Immune Factors at Play during Mycobacterium tuberculosis Infection of Macrophages

et al. 2022

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Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M.tb), is responsible for >1.5 million deaths worldwide annually. Innate immune cells, especially macrophages, are the first to encounter M.tb, and their response dictates the course of infection. During infection, macrophages exert a variety of immune factors involved in either controlling or promoting the growth of M.tb. Research on this topic has been performed in both in vitro and in vivo animal models with discrepant results in some cases based on the model of study. Herein, we review macrophage resistance and susceptibility immune factors, focusing primarily on recent advances in the field. We include macrophage cellular pathways, bioeffector proteins and molecules, cytokines and chemokines, associated microbiological factors and bacterial strains, and host genetic factors in innate immune genes. Recent advances in mechanisms underlying macrophage resistance and susceptibility factors will aid in the successful development of host-directed therapeutics, a topic emphasized throughout this review.

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CLEC4E (Mincle) genetic variation associates with pulmonary tuberculosis in Guinea-Bissau (West Africa)

Cited by 7 publications

References 45 publications

The kinetics of signaling through the common FcRγ chain determine cytokine profiles in dendritic cells

The kinetics of signaling through the common FcRγ chain determine cytokine profiles in dendritic cells

Polymorphisms in Immune Genes and Their Association with Tuberculosis Susceptibility: An Analysis of the African Population

Resistance and Susceptibility Immune Factors at Play during Mycobacterium tuberculosis Infection of Macrophages

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