scholarly journals Recognition of Staphylococcus aureus by the Innate Immune System

2005 ◽  
Vol 18 (3) ◽  
pp. 521-540 ◽  
Author(s):  
Bénédicte Fournier ◽  
Dana J. Philpott
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Protein A ◽  
Lipoteichoic Acid ◽  
Innate Immune ◽  
Peptidoglycan Recognition Protein ◽  
Recognition Protein ◽  
Necrosis Factor

SUMMARY The gram-positive bacterium Staphylococcus aureus is a major pathogen responsible for a variety of diseases ranging from minor skin infections to life-threatening conditions such as sepsis. Cell wall-associated and secreted proteins (e.g., protein A, hemolysins, and phenol-soluble modulin) and cell wall components (e.g., peptidoglycan and alanylated lipoteichoic acid) have been shown to be inflammatory, and these staphylococcal components may contribute to sepsis. On the host side, many host factors have been implicated in the innate detection of staphylococcal components. One class of pattern recognition molecules, Toll-like receptor 2, has been shown to function as the transmembrane component involved in the detection of staphylococcal lipoteichoic acid and phenol-soluble modulin and is involved in the synthesis of inflammatory cytokines by monocytes/macrophages in response to these components. Nod2 (nucleotide-binding oligomerization domain 2) is the intracellular sensor for muramyl dipeptide, the minimal bioactive structure of peptidoglycan, and it may contribute to the innate immune defense against S. aureus. The staphylococcal virulence factor protein A was recently shown to interact directly with tumor necrosis factor receptor 1 in airway epithelium and to reproduce the effects of tumor necrosis factor alpha. Finally, peptidoglycan recognition protein L is an amidase that inactivates the proinflammatory activities of peptidoglycan. However, peptidoglycan recognition protein L probably plays a minor role in the innate immune response to S. aureus. Thus, several innate immunity receptors may be implicated in host defense against S. aureus.

scholarly journals Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection

2013 ◽  
Vol 81 (11) ◽  
pp. 4200-4207 ◽  
Author(s):  
Constanza Giai ◽  
Cintia Gonzalez ◽  
Camila Ledo ◽  
Ailin Garofalo ◽  
María Silvia Di Genaro ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Protein A ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTStaphylococcus aureusinfections are an important public health concern due to their increasing incidence and high rates of mortality. The success ofS. aureusas a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-α) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients.S. aureusprotein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-α receptor 1 (TNFR1). In this study, we demonstrate thatS. aureus, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-αin vitroandin vivo. The results obtained using a protein A-deficient mutant andtnfr1−/−mice strongly suggest that the increased levels of soluble TNFR1 present during experimentalS. aureusinfection may neutralize circulating TNF-α and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by whichS. aureussubverts the host immune response.

scholarly journals Peptidoglycan and Lipoteichoic Acid from Staphylococcus aureus Induce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a Human Whole Blood Model

2000 ◽  
Vol 68 (7) ◽  
pp. 3965-3970 ◽  
Author(s):  
J. E. Wang ◽  
P. F. Jørgensen ◽  
M. Almlöf ◽  
C. Thiemermann ◽  
S. J. Foster ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Lipoteichoic Acid ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We have examined the ability of peptidoglycan (PepG) and lipoteichoic acid (LTA) isolated from Staphylococcus aureusto induce the release of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-10 in whole human blood and identified the cellular origins of these cytokines. Both PepG and LTA induced transient increases in TNF-α and IL-10 in plasma, with peak values at 6 and 12 h, respectively. IL-6 values increased throughout the experimental period (24 h). The TNF-α, IL-6, and IL-10 release induced by PepG and LTA was dose dependent. Only PepG was a potent inducer of TNF-α secretion. After stimulation of whole blood with PepG or LTA, very pure populations of monocytes (CD14 positive), T cells (CD2 positive), B cells (CD19 positive), and granulocytes (CD15 positive) were isolated by immunomagnetic separation and analyzed by reverse transcription-PCR for mRNA transcripts encoding TNF-α, IL-6, and IL-10. The TNF-α mRNA results were inconclusive. In contrast, PepG induced IL-6 and IL-10 mRNA accumulation in both T cells and monocytes. LTA, as well as lipopolysaccharide, induced IL-6 and IL-10 mRNA production in monocytes and possibly in T cells. Whether granulocytes and B cells produce cytokines in response to bacterial stimuli remains obscure. Blockade of the CD14 receptors with monoclonal antibodies (18D11) had no influence on the PepG-induced release of TNF-α but attenuated the LTA-induced release of the same cytokine. In conclusion, our data indicate that circulating T cells and monocytes contribute to cytokine production in sepsis caused by gram-positive bacteria.

scholarly journals Human Immunodeficiency Virus Infection Alters Tumor Necrosis Factor Alpha Production via Toll-Like Receptor-Dependent Pathways in Alveolar Macrophages and U1 Cells

2008 ◽  
Vol 82 (16) ◽  
pp. 7790-7798 ◽  
Author(s):  
Marlynne Q. Nicol ◽  
Jean-Marie Mathys ◽  
Albertina Pereira ◽  
Kevin Ollington ◽  
Michael H. Ieong ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Innate Immune ◽  
Hiv Positive ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy. The reasons for this are unclear but may involve changes in innate immune function. HIV type 1 infection of macrophages impairs effector functions, including cytokine production. We observed decreased constitutive tumor necrosis factor alpha (TNF-α) concentrations and increased soluble tumor necrosis factor receptor type II (sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects compared to healthy controls. Moreover, net proinflammatory TNF-α activity, as measured by the TNF-α/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-α is an important component of the innate immune system and is produced upon activation of Toll-like receptor (TLR) pathways, we hypothesized that the mechanism associated with deficient TNF-α production in the lung involved altered TLR expression or a deficit in the TLR signaling cascade. We found decreased Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1 monocytic cells compared to the uninfected parental U937 cell line and decreased TLR message in alveolar macrophages (AMs) from HIV-positive subjects. In addition, stimulation with TLR1/2 ligand (Pam3Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-α in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-α production in response to these TLR2 and TLR4 ligands. We postulate that HIV infection alters expression of TLRs with subsequent changes in mitogen-activated protein kinase signaling and cytokine production that ultimately leads to deficiencies of innate immune responses that predispose HIV-positive subjects to infection.

scholarly journals Tumor Necrosis Factor (TNF) Receptor Shedding Controls Thresholds of Innate Immune Activation That Balance Opposing TNF Functions in Infectious and Inflammatory Diseases

2004 ◽  
Vol 200 (3) ◽  
pp. 367-376 ◽  
Author(s):  
Sofia Xanthoulea ◽  
Manolis Pasparakis ◽  
Stavroula Kousteni ◽  
Cord Brakebusch ◽  
David Wallach ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Bacterial Infections ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Endotoxic Shock ◽  
Innate Immune ◽  
Disease Assessment ◽  
Recurrent Fever ◽  
Receptor Shedding ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated. One of the mechanisms that may have evolved to modulate TNF function is the proteolytic cleavage of its cell surface receptors. In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation. Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor–dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections. Notably, gain of function for antibacterial host defenses ensues at the cost of disbalanced inflammatory reactions that lead to pathology. Mutant mice exhibit spontaneous hepatitis, enhanced susceptibility to endotoxic shock, exacerbated TNF-dependent arthritis, and experimental autoimmune encephalomyelitis. These results introduce a new concept for receptor shedding as a mechanism setting up thresholds of cytokine function to balance resistance and susceptibility to disease. Assessment of p55TNFR shedding may thus be of prognostic value in infectious, inflammatory, and autoimmune diseases.

scholarly journals Mycobacterium marinumLipooligosaccharides Are Unique Caryophyllose-containing Cell Wall Glycolipids That Inhibit Tumor Necrosis Factor-α Secretion in Macrophages

2009 ◽  
Vol 284 (31) ◽  
pp. 20975-20988 ◽  
Author(s):  
Yoann Rombouts ◽  
Adeline Burguière ◽  
Emmanuel Maes ◽  
Bernadette Coddeville ◽  
Elisabeth Elass ◽  
...  
Keyword(s):  
Cell Wall ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inhibit Tumor Necrosis Factor
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