Mycobacterial Trehalose 6,6′-Dimycolate–Induced M1-Type Inflammation

Nguyen, Trang; d’Aigle, John; Chinea, Luis E.; Niaz, Zainab; Hunter, Robert L.; Hwang, Shen-An; Actor, Jeffrey K.

doi:10.1016/j.ajpath.2019.10.006

Cited by 14 publications

(12 citation statements)

References 59 publications

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“…impairing the acidification of phagosomes, subverting the bactericidal activities in infected macrophages, and promoting rapid disease progression in a murine model of TB [16][17][18][19] . It is important to note that Mtb isolated from the pulmonary cavities and exhaled air of TB patients have a cording phenotype 3,11,20 .…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note that Mtb isolated from the pulmonary cavities and exhaled air of TB patients have a cording phenotype 3,11,20 . Mtb aggregates contain elevated levels of trehalose 6,6' dimycolate, a major glycolipid present in the bacillary cell wall, which induces M1-type inflammation very early during Mtb infection of macrophages and contributes to necrotic granuloma formation in infected mice 17,21 . These studies support our finding that Mtb-AG can cause severe inflammation and host cell destruction, resulting in larger, necrotic granulomas in infected rabbit lungs.…”

Section: Discussionmentioning

confidence: 99%

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Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

et al. 2021

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In vitro phagocytosis of Mycobacterium tuberculosis (Mtb) aggregates (Mtb-AG), rather than similar numbers of single bacilli (Mtb-SC), induces host macrophage death and favors bacterial growth. Here, we examined whether aggregation contributes to enhanced Mtb pathogenicity in vivo in rabbit lungs. Rabbits were exposed to infectious aerosols containing mainly Mtb-AG or Mtb-SC. The lung bacterial load, systemic immune response, histology, and immune cell composition were investigated over time. Genome-wide transcriptome analysis, cellular and tissue-level assays, and immunofluorescent imaging were performed on lung tissue to define and compare immune activation and pathogenesis between Mtb-AG and Mtb-SC infection. Lung bacillary loads, disease scores, lesion size, and structure were significantly higher in Mtb-AG than Mtb-SC infected animals. Differences in immune cell distribution and activation were noted in the lungs of the two groups of infected animals. Consistently larger lung granulomas with large aggregates of Mtb, extensive necrotic foci, and elevated matrix metalloproteases expression were observed in Mtb-AG infected rabbits. Our findings suggest that bacillary aggregation increases Mtb fitness for improved growth and accelerates lung inflammation and infected host cell death, thereby exacerbating disease pathology in the lungs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

et al. 2021

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“…In murine models of Mycobacterium tuberculosis (Mtb) infection, TDM administration drove the early pro-inflammatory M1-like macrophage response related to the granulomas of primary pathology; proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-12p40 were produced in lung tissue [ 74 ]. Furthermore, CD11b+CD45+ macrophages with a high surface expression of the pro-inflammatory CD38 and CD86 markers were found in lung lesions of mice at 7 days post-TDM introduction, but low phenotypic marker expression of anti-inflammatory M2-like markers CD206 and EGR-2 were present on macrophages.…”

Section: Assemblies From Cationic Lipids and Surfactantsmentioning

confidence: 99%

“…TDM played a role in establishment of the M1-like shift in the microenvironment during primary tuberculosis. Thus, the MTB cell wall cording factor TDM is a physiologically relevant and useful molecule for modeling early macrophage-mediated events during establishment of the tuberculosis-induced granuloma pathogenesis [ 74 ].…”

Section: Assemblies From Cationic Lipids and Surfactantsmentioning

confidence: 99%

Cationic Nanostructures for Vaccines Design

Carmona-Ribeiro

Betancourt

2020

Biomimetics

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Subunit vaccines rely on adjuvants carrying one or a few molecular antigens from the pathogen in order to guarantee an improved immune response. However, to be effective, the vaccine formulation usually consists of several components: an antigen carrier, the antigen, a stimulator of cellular immunity such as a Toll-like Receptors (TLRs) ligand, and a stimulator of humoral response such as an inflammasome activator. Most antigens are negatively charged and combine well with oppositely charged adjuvants. This explains the paramount importance of studying a variety of cationic supramolecular assemblies aiming at the optimal activity in vivo associated with adjuvant simplicity, positive charge, nanometric size, and colloidal stability. In this review, we discuss the use of several antigen/adjuvant cationic combinations. The discussion involves antigen assembled to 1) cationic lipids, 2) cationic polymers, 3) cationic lipid/polymer nanostructures, and 4) cationic polymer/biocompatible polymer nanostructures. Some of these cationic assemblies revealed good yet poorly explored perspectives as general adjuvants for vaccine design.

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“…Studies have shown that macrophage-derived C-type lectin can recognize TDM(trehalose 6,6'dimycolate) and activate NF-kippa B signaling [20,25,27]. TDM is a surface antigen of bacteria such as mycobacterium, which can be recognized by C-type lectin and induce the immune response of macrophages [28,29]. TDM also can induce pneumonia and activate the immune function of Th cells [30,31].…”

Section: Changing Of Expression Profile Of C-type Lecin Family Indicamentioning

confidence: 99%

Activating organ’s immunizing power against COVID–19–learning from SARS

Wang

Xia²

2020

Preprint

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Background Coronaviruses cause respiratory diseases in many animals, including humans.Spike protein is an important component of coronavirus structure and the formation of ACE2 (angiotensin converting enzyme 2)-spike complex mediates virus entry to host cells.C-type lectin family are widely distribute on the surface of human cells and have been shown to activate the immune system. In this article, we first illustrate why we can "learn from SARS" with phylogenetic analysis. Then, we use SARS spike protein structure, to inferring our molecular docking experiment, revealing the potential capacity of C-type lectin to directly interact with spike protein obstructs the formation of spike-ACE2 complex. Considering the expression profile of C-type lectin family changing significantly during infection, we predict certain members of this kind of protein as potential therapeutic target and verify their assumed function by inferring an C-type lectindependent CD4/CD28 T cell survival molecular network with endogenous molecular network theory (EMT) and comparing the predicted expression trend corresponding to each molecular with experiment data. Methods Alignments are inferred by MAFFT V7 ( G-ins-i, Blosom). Maximum likelihood analyses and bootstrap test carried out by RAXML V8.2 ML+BP online platform. Protein structure is predicted by SWISSMODELLING online platform. Molecular docking experiment is carried out by Z-dock Version 3.0.2. C-type lectin-dependent CD4/CD28 T cell Network is inferred by EMT theory.Result Our molecular docking experiment revealing the potential capacity of C-type lectin to directly interact with spike protein obstructs the formation of spike-ACE2 complex.Based on the expression profile of C-type lectin family during infection, we predicting certain member of this kind of protein as potential therapeutic target such as Clec7a, Clec12a and Clec11a, corresponding immune cell types such as CD4/CD28 T Yi Wang conceived the project, designed the experiment and wrote the manuscript.Chuanxin Xia wrote the manuscript. All authors read and approved the final manuscript. AcknowledgementThanks for my sister's kindly help.Hoping this work can inspiring fellow scientists for related experiment design and improving people's confidence in overcoming SARI.

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Mycobacterial Trehalose 6,6′-Dimycolate–Induced M1-Type Inflammation

Cited by 14 publications

References 59 publications

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

Cationic Nanostructures for Vaccines Design

Activating organ’s immunizing power against COVID–19–learning from SARS

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