Selective Activation of Human Intestinal Mast Cells by <i>Escherichia coli</i> Hemolysin

Krämer, Sigrid; Sellge, Gernot; Lorentz, Axel; Krueger, Dagmar; Schemann, Michael; Feilhauer, Katharina; Gunzer, Florian; Bischoff, Stephan C.

doi:10.4049/jimmunol.181.2.1438

Cited by 35 publications

(33 citation statements)

References 45 publications

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“…Ex vivo, in the lamina propria of human intestinal tissue, histamine secretion in response to E. coli was HlyA dependent, consistent with an increased degranulation of mast cells. This was also found in vitro, where mast cell activation was dependent on Ca 2ϩ influx and p38 and ERK MAPKs (349). In renal epithelial cells in vitro, HlyA was found to induce a constant, low-frequency calcium oscillation response.…”

Section: Innate Immune Responses To Pftsmentioning

confidence: 51%

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

350

351

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SUMMARY Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae , group A and B streptococci, Staphylococcus aureus , Escherichia coli , and Mycobacterium tuberculosis . PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo . This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.

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Section: Innate Immune Responses To Pftsmentioning

confidence: 51%

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

350

351

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“…Thus, activation of PAR-2 expressed by mast cells (19,55) may participate in the recruitment of these cells. Mast cells can be activated by bacterial antigens (33,35,53), leading to the release of inflammatory mediators that are pivotal to the innate immune response (20,22,54). These cells may therefore play a pivotal role in the early inflammatory response to P. gingivalis in chronic periodontitis.…”

Section: Vol 78 2010 Role Of Par-2 In Periodontitis 635mentioning

confidence: 99%

Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis

et al. 2010

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The tissue destruction seen in chronic periodontitis is commonly accepted to involve extensive upregulation of the host inflammatory response. Protease-activated receptor 2 (PAR-2)-null mice infected with Porphyromonas gingivalis did not display periodontal bone resorption in contrast to wild-type-infected and PAR-1-nullinfected mice. Histological examination of tissues confirmed the lowered bone resorption in PAR-2-null mice and identified a substantial decrease in mast cells infiltrating the periodontal tissues of these mice. T cells from P. gingivalis-infected or immunized PAR-2-null mice proliferated less in response to antigen than those from wild-type animals. CD90 (Thy1.2) expression on CD4؉ and CD8 ؉ T-cell-receptor ␤ (TCR␤) T cells was significantly (P < 0.001) decreased in antigen-immunized PAR-2-null mice compared to sham-immunized PAR-2-null mice; this was not observed in wild-type controls. T cells from infected or antigen-immunized PAR-2-null mice had a significantly different Th1/inflammatory cytokine profile from wild-type cells: in particular, gamma interferon, interleukins (interleukin-2, -3, and -17), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha demonstrated lower expression than wild-type controls. The absence of PAR-2 therefore appears to substantially decrease T-cell activation and the Th1/inflammatory response. Regulation of such proinflammatory mechanisms in T cells and mast cells by PAR-2 suggests a pivotal role in the pathogenesis of the disease.

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“…After the exposure by harmless Ag such as ragweed pollen for sensitization, Ag-specific IgE-bound FcεRI are cross-linked, and then mast cell granules are released (9,10). As well, invasion by harmful microbes or exposure to the components of bacteria (11)(12)(13), hyphae (14), or toxins generated by infecting microbes (15)(16)(17) also lead to mast cell degranulation. As a result, many of the mediators in the granules, including b-hexosaminidase, spread through the tissues, triggering typical allergic reactions for exclusion of harmless Ag or the inflammatory response designed to eliminate harmful substances (9).…”

mentioning

confidence: 99%

Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

Fukuishi

Murakami

Ohno

et al. 2014

The Journal of Immunology

102

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β-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of β-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC β-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of β-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or β-hexosaminidase gene–deficient (hexb−/−-BMMC) mice were transplanted into MC-deficient (WBB6F1/J-KitW/KitW-v [W/Wv]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/Wv, BL/6-BMMC–reconstituted W/Wv, or hexb−/−-BMMC–reconstituted W/Wv mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/Wv and hexb−/−-BMMC–reconstituted W/Wv mice than in BL/6 and BL/6-BMMC–reconstituted W/Wv mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb−/−-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb−/−-BMMC lysate plus β-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb−/−-BMMC lysate. These findings strongly suggest that MC granule β-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of β-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.

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Selective Activation of Human Intestinal Mast Cells by Escherichia coli Hemolysin

Cited by 35 publications

References 45 publications

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis

Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

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