Faculty Opinions recommendation of Human mast cell activation by Staphylococcus aureus: interleukin-8 and tumor necrosis factor alpha release and the role of Toll-like receptor 2 and CD48 molecules.

ABSTRACT Amphotericin B (AmB) is a ligand of toll-like receptor 2 (TLR2). Here, we demonstrate the participation of TLR1 in AmB-induced cell activation that led to the secretion of tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-8. Hence, TLR2-TLR1 coactivation serves as the underlying mechanism for the proinflammatory toxicities associated with AmB.

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Macrophage-Elicited Osteoclastogenesis in Response to Bacterial Stimulation Requires Toll-Like Receptor 2-Dependent Tumor Necrosis Factor-Alpha Production

Infection and Immunity ◽

10.1128/iai.01241-07 ◽

2007 ◽

Vol 76 (2) ◽

pp. 812-819 ◽

Cited By ~ 52

Author(s):

Takashi Ukai ◽

Hiromichi Yumoto ◽

Frank C. Gibson ◽

Caroline Attardo Genco

Keyword(s):

Tumor Necrosis Factor ◽

Cell Surface ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Toll Like Receptor ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Toll Like Receptor 2 ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT The receptor activator of NF-κB ligand (RANKL) and the proinflammatory cytokines are believed to play important roles in osteoclastogenesis. We recently reported that the innate immune recognition receptor, Toll-like receptor 2 (TLR2), is crucial for inflammatory bone loss in response to infection by Porphyromonas gingivalis, the primary organism associated with chronic inflammatory periodontal disease. However, the contribution of macrophage-expressed TLRs to osteoclastogenesis has not been defined. In this study, we defined a requirement for TLR2 in tumor necrosis factor-alpha (TNF-α)-elicited osteoclastogenesis in response to exposure to P. gingivalis. Culture supernatant (CS) fluids from P. gingivalis-stimulated macrophages induced bone marrow macrophage-derived osteoclastogenesis. This activity was dependent on TNF-α and occurred independently of RANKL, interleukin-1β (IL-1β), and IL-6. CS fluids from P. gingivalis-stimulated TLR2−/− macrophages failed to express TNF-α, and these fluids induced significantly less osteoclast formation compared with that of the wild-type or the TLR4−/− macrophages. In addition, P. gingivalis exposure induced up-regulation of TLR2 expression on the cell surface of macrophages, which was demonstrated to functionally react to reexposure to P. gingivalis, as measured by a further increase in TNF-α production. These results demonstrate that macrophage-dependent TLR2 signaling is crucial for TNF-α-dependent/RANKL-independent osteoclastogenesis in response to P. gingivalis infection. Furthermore, the ability of P. gingivalis to induce the cell surface expression of TLR2 may contribute to the chronic inflammatory state induced by this pathogen.

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Glucocorticoids and Tumor Necrosis Factor Alpha Cooperatively Regulate Toll-Like Receptor 2 Gene Expression

Molecular and Cellular Biology ◽

10.1128/mcb.24.11.4743-4756.2004 ◽

2004 ◽

Vol 24 (11) ◽

pp. 4743-4756 ◽

Cited By ~ 102

Author(s):

Marcela A. Hermoso ◽

Tetsuya Matsuguchi ◽

Kathleen Smoak ◽

John A. Cidlowski

Keyword(s):

Innate Immunity ◽

Transcription Factors ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Toll Like Receptor ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Toll Like Receptor 2 ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) and glucocorticoids are widely recognized as mutually antagonistic regulators of adaptive immunity and inflammation. Surprisingly, we show here that they cooperatively regulate components of innate immunity. The Toll-like receptor 2 (TLR2) gene encodes a transmembrane receptor critical for triggering innate immunity. Although TLR2 mRNA and protein are induced by inflammatory molecules such as TNF-α, we show that TLR2 is also induced by the anti-inflammatory glucocorticoids in cells where they also regulate MKP-1 mRNA and protein levels. TNF-α and glucocorticoids cooperate to regulate the TLR2 promoter, through the involvement of a 3′ NF-κB site, a STAT-binding element, and a 3′ glucocorticoid response element (GRE). Molecular studies show that the IκBα superrepressor or a STAT dominant negative element prevented TNF-α and dexamethasone stimulation of TLR2 promoter. Similarly, an AF-1 deletion mutant of glucocorticoid receptor or ablation of a putative GRE notably reduced the cooperative regulation of TLR2. Using chromatin immunoprecipitation assays, we demonstrate that all three transcription factors interact with both endogenous and transfected TLR2 promoters after stimulation by TNF-α and dexamethasone. Together, these studies define novel signaling mechanism for these three transcription factors, with a profound impact on discrimination of innate and adaptive immune responses.

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Human Mast Cell Activation by Staphylococcus aureus: Interleukin-8 and Tumor Necrosis Factor Alpha Release and the Role of Toll-Like Receptor 2 and CD48 Molecules

Infection and Immunity ◽

10.1128/iai.00270-08 ◽

2008 ◽

Vol 76 (10) ◽

pp. 4489-4497 ◽

Cited By ~ 62

Author(s):

Claudio M. Rocha-de-Souza ◽

Beata Berent-Maoz ◽

David Mankuta ◽

Allon E. Moses ◽

Francesca Levi-Schaffer

Keyword(s):

Staphylococcus Aureus ◽

Mast Cells ◽

Tumor Necrosis ◽

Toll Like Receptor ◽

Atopic Diseases ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Toll Like Receptor 2 ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT The ability of Staphylococcus aureus to invade and survive within host cells is believed to contribute to its propensity to cause persistent and metastatic infections. In addition, S. aureus infections often are associated with atopic diseases such as dermatitis, rhinitis, and asthma. Mast cells, the key cells of allergic diseases, have a pivotal role in innate immunity and have the capacity of phagocytosis, and they can destroy some pathogenic bacteria. However, little is known about the ability of some other bacteria to survive and overcome mast cell phagocytosis. Therefore, we were interested in evaluating the interplay between mast cells and S. aureus. In this study, we show that human cord blood-derived mast cells (CBMC) can be infected by pathogenic S. aureus. S. aureus displayed a high adherence to mast cells as well as invasive and survival abilities within them. However, when infections were performed in the presence of cytochalasin D or when CBMC were preincubated with anti-Toll-like receptor 2 (TLR2) or anti-CD48 antibodies, the invasiveness and the inflammatory response were abrogated, respectively. Furthermore, we observed an increase of TLR2 and CD48 molecules on CBMC after S. aureus infection. The infection of CBMC with S. aureus also caused the release of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). Both live and killed S. aureus organisms were found to trigger TNF-α and IL-8 release by CBMC in a time-dependent manner. Cumulatively, these findings suggest that S. aureus internalizes and survives in mast cells. This may play an important role in infections and in atopic diseases associated with S. aureus.

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Lipoteichoic Acids from Lactobacillus Strains Elicit Strong Tumor Necrosis Factor Alpha-Inducing Activities in Macrophages through Toll-Like Receptor 2

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.2.259-266.2003 ◽

2003 ◽

Vol 10 (2) ◽

pp. 259-266 ◽

Cited By ~ 156

Author(s):

Tetsuya Matsuguchi ◽

Akimitsu Takagi ◽

Takeshi Matsuzaki ◽

Masato Nagaoka ◽

Kimika Ishikawa ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Toll Like Receptor ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Toll Like Receptor 2 ◽

Factor Alpha ◽

Necrosis Factor ◽

Lipoteichoic Acids

ABSTRACT Lactobacilli are nonpathogenic gram-positive inhabitants of microflora. At least some Lactobacillus strains have been postulated to have health beneficial effects, such as the stimulation of the immune system. Here we examined the stimulatory effects of lactobacilli on mouse immune cells. All six heat-killed Lactobacillus strains examined induced the secretion of tumor necrosis factor alpha (TNF-α) from mouse splenic mononuclear cells, albeit to various degrees. When fractionated subcellular fractions of Lactobacillus casei were tested for NF-κB activation and TNF-α production in RAW264.7, a mouse macrophage cell line, the activity was found to be as follows: protoplast > cell wall ≫ polysaccharide-peptidoglycan complex. Both crude extracts and purified lipoteichoic acids (LTAs) from two Lactobacillus strains, L. casei and L. fermentum, significantly induced TNF-α secretion from RAW264.7 cells and splenocytes of C57BL/6, C3H/HeN, and C3H/HeJ mice but not from splenocytes of C57BL/6 TLR2 −/− mice. Lactobacillus LTA induced activation of c-Jun N-terminal kinase activation in RAW264.7 cells. Furthermore, in HEK293T cells transected with a combination of CD14 and Toll-like receptor 2 (TLR2), NF-κB was activated in response to Lactobacillus LTA. Taken together, these data suggest that LTAs from lactobacilli elicit proinflammatory activities through TLR2.

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