Identification of anti-lipoarabinomannan antibodies against mannan core and their effects on phagocytosis of mycobacteria by human neutrophils

Nakayama, Hitoshi; Oshima, Eriko; Hotta, Tomomi; Hanafusa, Kei; Nakamura, Kota; Yokoyama, Noriko; Ogawa, Hideoki; Takamori, Kenji; Iwabuchi, Kazuhisa

doi:10.1016/j.tube.2022.102165

Cited by 7 publications

(5 citation statements)

References 61 publications

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“…Recently, Hitoshi et al identified that the anti-lipoarabinomannan (anti-LAM) monoclonal IgMs, TMDU3 and LA066, significantly inhibited the phagocytosis of Mycobacterium avium by human neutrophils, and that mycobacterial load was reduced in the presence of neutrophils and anti-LAM IgM (albeit in the absence of other opsonins). These mannan core-directed monoclonal antibodies (mAbs) were therefore proposed as potential therapies to target aberrant or excessive neutrophil-associated immune responses [ 136 ].…”

Section: Introductionmentioning

confidence: 99%

The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease

Alkarni

Lipman

Lowe

2023

Ann Clin Microbiol Antimicrob

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Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils’ capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections.

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Section: Introductionmentioning

confidence: 99%

The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease

Alkarni

Lipman

Lowe

2023

Ann Clin Microbiol Antimicrob

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“…The binding of LAM to lactosylceramide (LacCer)-enriched lipid domains will lead to phagocytosis of the neutrophils. Nakayama et al investigated the specificity of binding of several anti-LAM IgMs, such as TMDU3 and La066, which are directed against the mannan core of LAM and strongly bind to Mtb [ 55 ].…”

Section: Lipoarabinomannan (Lam) Biosynthesismentioning

confidence: 99%

“…Furthermore, treatment with these antibodies has been shown to reduce the Mtb intracellular presence in human neutrophils. This indicates that the blockage of LacCer-enriched lipid micro-domains and LAM interaction can be a possible therapeutic and/or diagnostic target for Mtb infection [ 55 ]. Moreover, it was recently demonstrated that LAM could induce lipid droplet (LD) formation and activation of PPARγ involving host surface receptors, for instance, TRLs, CD36, CD14, and CD11b/Cd18.…”

Section: Lipoarabinomannan (Lam) Biosynthesismentioning

confidence: 99%

Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection

Italia,

Shaik,

Peri

2023

Biomolecules

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Emerging pharmacological strategies that target major virulence factors of antibiotic-resistant Mycobacterium tuberculosis (Mtb) are presented and discussed. This review is divided into three parts corresponding to structures and functions important for Mtb pathogenicity: the cell wall, the lipoarabinomannan, and the secretory proteins. Within the cell wall, we further focus on three biopolymeric sub-components: mycolic acids, arabinogalactan, and peptidoglycan. We present a comprehensive overview of drugs and drug candidates that target cell walls, envelopes, and secretory systems. An understanding at a molecular level of Mtb pathogenesis is provided, and potential future directions in therapeutic strategies are suggested to access new drugs to combat the growing global threat of antibiotic-resistant Mtb infection.

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“…Monoclonal antibodies (mAbs) that recognize LAM or LM can be used, 15,16 yet an antibody's size (180 kDa) can limit its utility for visualizing the LAM (15 kDa) as structural occlusion of other membrane components can complicate in cellulo analyses. 17,18 Thus, new strategies are needed for the selective structural perturbation of mannosecontaining glycans to probe their composition, function, and dynamics within the context of live cells and disease pathogenesis. 19 Our understanding of the roles of these mannose derivatives would be enhanced by methods to visualize them.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Despite the importance of these glycolipids, few direct methods exist to study their biosynthesis, trafficking, and biological function. Monoclonal antibodies (mAbs) that recognize LAM or LM can be used, , yet an antibody’s size (180 kDa) can limit its utility for visualizing the LAM (15 kDa) as structural occlusion of other membrane components can complicate in cellulo analyses. , Thus, new strategies are needed for the selective structural perturbation of mannose-containing glycans to probe their composition, function, and dynamics within the context of live cells and disease pathogenesis …”

Section: Introductionmentioning

confidence: 99%

Selective Glycan Labeling of Mannose-Containing Glycolipids in Mycobacteria

Lee,

Marando,

Smelyansky

et al. 2023

J. Am. Chem. Soc.

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Mycobacterium tuberculosis (Mtb) is one of history's most successful human pathogens. By subverting typical immune responses, Mtb can persist within a host until conditions become favorable for growth and proliferation. Virulence factors that enable mycobacteria to modulate host immune systems include a suite of mannose-containing glycolipids: phosphatidylinositol mannosides, lipomannan, and lipoarabinomannan (LAM). Despite their importance, tools for their covalent capture, modification, and imaging are limited. Here, we describe a chemical biology strategy to detect and visualize these glycans. Our approach, biosynthetic incorporation, is to synthesize a lipid-glycan precursor that can be incorporated at a latestage step in glycolipid biosynthesis. We previously demonstrated selective mycobacterial arabinan modification by biosynthetic incorporation using an exogenous donor. This report reveals that biosynthetic labeling is general and selective: it allows for cell surface mannose-containing glycolipid modification without nonspecific labeling of mannosylated glycoproteins. Specifically, we employed azido-(Z,Z)-farnesyl phosphoryl-β-D-mannose probes and took advantage of the strain-promoted azide−alkyne cycloaddition to label and directly visualize the localization and dynamics of mycobacterial mannose-containing glycolipids. Our studies highlight the generality and utility of biosynthetic incorporation as the probe structure directs the selective labeling of distinct glycans. The disclosed agents allowed for direct tracking of the target immunomodulatory glycolipid dynamics in cellulo. We anticipate that these probes will facilitate investigating the diverse biological roles of these glycans.

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Identification of anti-lipoarabinomannan antibodies against mannan core and their effects on phagocytosis of mycobacteria by human neutrophils

Cited by 7 publications

References 61 publications

The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease

The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease

Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection

Selective Glycan Labeling of Mannose-Containing Glycolipids in Mycobacteria

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