Human Eosinophil Peroxidase Induces Surface Alteration, Killing, and Lysis of<i>Mycobacterium tuberculosis</i>

Borelli, Violetta; Vita, Francesca; Shankar, Sandeep; Soranzo, Maria Rosa; Banfi, Elena; Scialino, Giuditta; Brochetta, Cristiana; Zabucchi, Giuliano

doi:10.1128/iai.71.2.605-613.2003

Cited by 57 publications

(46 citation statements)

References 49 publications

(33 reference statements)

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“…4D), suggesting a role for both VEGF and neutrophils in the vascularization of adherent matrices. Although the granule protein eosinophil peroxidase has inhibitory activity toward M. tuberculosis H37Rv in vitro, the presence of eosinophils in pulmonary models of tuberculosis is considered detrimental as they are reflective of a harmful T H 2 cytokine profile and contribute to tissue necrosis (41)(42)(43). Eosinophil recruitment was noted in response to trehalose mycolates, and likely reflects a lack of T H 1-bias in the cytokine profile of matrices.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

Geisel

Sakamoto

Russell

et al. 2005

The Journal of Immunology

171

154

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The hallmark of Mycobacterium-induced pathology is granulomatous inflammation at the site of infection. Mycobacterial lipids are potent immunomodulators that contribute to the granulomatous response and are released in appreciable quantities by intracellular bacilli. Previously we investigated the granulomagenic nature of the peripheral cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin (BCG) by coating the lipids onto 90-μm diameter microspheres that were mixed into Matrigel matrix with syngeneic bone marrow-derived macrophages and injected i.p. into mice. These studies demonstrated that BCG lipids elicit proinflammatory cytokines and recruit leukocytes. In the current study we determined the lipids responsible for this proinflammatory effect. BCG-derived cell wall lipids were fractionated and purified by liquid chromatography and preparative TLC. The isolated fractions including phosphatidylinositol dimannosides, cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, trehalose monomycolate, trehalose dimycolate, and mycoside B. Trehalose dimycolate, when delivered to bone marrow-derived murine macrophages, induced the greatest secretion of IL-1β, IL-6, and TNF-α in vitro. Trehalose dimycolate similarly induced the greatest secretion of these proinflammatory cytokines in ex vivo matrices over the course of 12 days. Trehalose monomycolate and dimycolate also induced profound neutrophil recruitment in vivo. Experiments with TLR2 or TLR4 gene-deficient mice revealed no defects in responses to trehalose mycolates, although MyD88-deficient mice manifested significantly reduced cell recruitment and cytokine production. These results demonstrate that the trehalose mycolates, particularly trehalose dimycolate, are the most bioactive lipids in the BCG extract, inducing a proinflammatory cascade that influences granuloma formation.

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Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

Geisel

Sakamoto

Russell

et al. 2005

The Journal of Immunology

171

154

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“…These results support previous data showing that MBP possesses potent antibacterial properties against E. coli and S. aureus, ECP possesses antibacterial activity against E. coli, and purified EPO, another granule protein, can kill Mycobacterium spp. in vitro (8,24,27). We advanced these findings to establish a similar role for mouse eosinophil granules in vitro and the ability of eosinophil granule proteins to enhance bacterial clearance in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, human eosinophils recognize and are activated by multiple bacterial species in vitro (8,37,47,52). Once activated, these cells secrete cytotoxic granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO), all of which have antibacterial properties in vitro (8,24,27). How-ever, little is known about the role of eosinophils in vivo during bacterial infection.…”

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confidence: 99%

Mouse Eosinophils Possess Potent Antibacterial Properties In Vivo

et al. 2009

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Eosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance of Pseudomonas aeruginosa introduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.

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“…In this regard, a recent report analyzing Siglec-F null mice revealed enhanced eosinophil infiltration and blood eosinophilia in response to allergen challenge, suggesting that Siglec-F is a negative regulator of eosinophil response to allergens (86). Eosinophils also contribute to an immune response against foreign pathogens, including binding, engulfment, and killing of microbes (1,15,19,32,36,83). While investigating the endocytic activity of Siglec-F, we observed efficient endocytosis of anti-Siglec antibody, high-affinity sialoside ligand probes, and Neisseria meningitidis bearing sialylated glycans.…”

mentioning

confidence: 99%

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

Tateno

Schur

et al. 2007

Molecular and Cellular Biology

116

109

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Sialic acid-binding immunoglobulin-like lectins (siglecs) are predominately expressed on immune cells. They are best known as regulators of cell signaling mediated by cytoplasmic tyrosine motifs and are increasingly recognized as receptors for pathogens that bear sialic acid-containing glycans. Most siglec proteins undergo endocytosis, an activity tied to their roles in cell signaling and innate immunity. Here, we investigate the endocytic pathways of two siglec proteins, CD22 (Siglec-2), a regulator of B-cell signaling, and mouse eosinophil Siglec-F, a member of the rapidly evolving CD33-related siglec subfamily that are expressed on cells of the innate immune system. CD22 exhibits hallmarks of clathrin-mediated endocytosis and traffics to recycling compartments, consistent with previous reports demonstrating its localization to clathrin domains. Like CD22, Siglec-F mediates endocytosis of anti-Siglec-F and sialoside ligands, a function requiring intact tyrosinebased motifs. In contrast, however, we find that Siglec-F endocytosis is clathrin and dynamin independent, requires ADP ribosylation factor 6, and traffics to lysosomes. The results suggest that these two siglec proteins have evolved distinct endocytic mechanisms consistent with roles in cell signaling and innate immunity.The siglec (sialic-acid binding immunoglobulin [Ig]-like lectins) proteins are subset of the Ig superfamily of cell recognition molecules that bind to sialic acid-containing glycans of cell surface glycoconjugates as ligands (27,78). Of the 13 human and 9 murine siglec proteins, 4 are highly conserved in mammalian species: sialoadhesin (Sn)/Siglec-1, CD22/Siglec-2, myelin-associated glycoprotein (MAG)/Siglec-4, and Siglec-15. The others comprise a rapidly evolving subfamily homologous to CD33/Siglec-4, known as the CD33-related siglec proteins. With two exceptions (MAG and Siglec-6) the siglec proteins are predominantly expressed in various white blood cells of the immune system (25,43,78,85). All contain a N-terminal V-set sugar-binding Ig domain, a variable number of additional C-set Ig domains, a transmembrane domain, and a cytoplasmic domain that typically contains tyrosine-based motifs implicated in regulation of cell signaling and endocytosis.Many of the siglec proteins contain one or more immunoreceptor tyrosine-based inhibitory motifs (ITIMs), (I/L/V)XYXX (L/V), suggesting that they play important roles as inhibitory receptors of cell signaling (25, 78), as exemplified by CD22, which is well documented as a regulator of B-cell receptor (BCR) signaling. Upon antigen binding to the BCR, the ITIMs of CD22 are quickly tyrosine phosphorylated and recruit protein tyrosine phosphatase SHP-1, which dephosphorylates the BCR and dampens the B-cell response, setting a threshold for B-cell activation (27,73).CD22 is also known to undergo endocytosis following ligation by anti-CD22 antibody (38, 64) or high-affinity multivalent-sialoside ligands (22). The tyrosine-based ITIMs of CD22 also fit the sorting signal YXXØ (where Ø is a hydrophobic...

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Human Eosinophil Peroxidase Induces Surface Alteration, Killing, and Lysis ofMycobacterium tuberculosis

Cited by 57 publications

References 49 publications

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

Mouse Eosinophils Possess Potent Antibacterial Properties In Vivo

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

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