Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004623 (bacterial infection)
 15,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus intermedius is a commensal associated with serious, deep-seated purulent infections in major organs, such as the brain and liver. Histone-like DNA binding protein (HLP) is an accessory architectural protein in a variety of bacterial cellular processes. In this study, we investigated the mechanisms of pro-inflammatory cytokine inductions in THP-1 cells by stimulation with recombinant HLP of S. intermedius (rSi-HLP). rSi-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1 beta and TNF-alpha) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). In addition to its physiological role in bacterial growth through DNA binding, these results indicate that Si-HLP can trigger a cascade of events that induce pro-inflammatory responses via ERK1/2 and JNK signal pathways, and suggest that bacterial HLP may contribute to the activation of host innate immunity during bacterial infection.
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PMID:Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways. 1788 18

Bacterial infection induces a shift to type 1 CD4 T cell subset in an infected host and this shift is important for protection of the host from disease development. Many researchers think that the shift is antigen-dependent, but we previously demonstrated an initial induction step for CD4 T cell subsets during Listeria monocytogenes (Lm) infection is antigen-independent. Although Listeria is a TLR2 ligand, the immune system of the Lm-infected host responded to the pathogen to induce expression of CD69 but not CD25 on CD4 T cells, CD8 T cells and B cells even in the absence of TLR2 or MyD88. The antigen-independent activation of type 1 CD4 T cells accelerate the clearance of pathogens by activating innate immune cells with type 1 cytokines. Type 1 CD4 T cells and CD8 T cells also collaborate to protect the host from intracellular Lm infection. Since CD8 T cells function mainly as cytotoxic T cells and CD69-positive CD8 T cells increase during Lm-infection, cytotoxic activity of CD8 T cells was evaluated during Lm-infection. Although CD8 T cells were activated to produce IFN-gamma, the cytotoxic function of CD8 T cells in Lymphocytic choriomeningitis virus (LCMV) p14 TCR-transgenic mouse was not augmented by Lm-infection. Therefore, Lm-infection differentially influences on cytokine production and cytotoxicity of CD8 T cells.
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PMID:Differential effect of Listeria monocytogenes infection on cytokine production and cytotoxicity of CD8 T cells. 1789 7

To define the role of lipoteichoic acid (LTA) in innate immunity to gram-positive bacteria, we investigated the production of tumor necrosis factor alpha (TNF-alpha) by macrophages stimulated with gram-positive bacterial culture supernatants (GPCSs) after their LTA was removed or inactivated. GPCSs were obtained from three gram-positive species (pneumococci, staphylococci, and group B streptococci) during the exponential growth phase (designated early GPCSs) or at the senescent stage (designated late GPCSs). LTA was removed using an anti-LTA antibody or was inactivated by alkaline hydrolysis or platelet-activating factor acetylhydrolase (PAF-AH) treatment. Both early and late GPCSs from the three gram-positive bacteria stimulated macrophages to produce TNF-alpha primarily via Toll-like receptor 2 (TLR2), although late pneumococcal supernatant could stimulate macrophages via TLR4 as well. Following LTA inactivation by both methods, early GPCS lost about 85 to 100% of its activity and late GPCS lost about 50 to 90%. Both early and late culture supernatants from Escherichia coli could be inactivated by alkali hydrolysis but not by PAF-AH. In addition, removal of LTA from an early staphylococcal culture supernatant with a monoclonal antibody reduced about 70 to 85% of its potency. Reconstitution of inactivated early GPCS with a highly purified LTA restored its inflammatory activity, but the restored GPCS had higher activity than the pure LTA alone. These findings indicate that LTA is the primary TLR2 ligand in the early phase of gram-positive bacterial infection and remains a major ligand in the late phase when another TLR2 and TLR4 ligand(s) appears. In addition, our findings suggest that another gram-positive bacterial factor(s) synergizes with LTA in inducing inflammatory responses.
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PMID:Lipoteichoic acid is important in innate immune responses to gram-positive bacteria. 1795 23

Lipoteichoic acid (LTA) is a major outer cell wall component of Gram-positive bacteria that has been implicated as an important factor in the inflammatory response following bacterial infection. In vitro data indicate roles for TLR2, platelet-activating factor receptor (PAFR), CD14, and LPS-binding protein (LBP) in cellular responsiveness to LTA, whereas the mechanisms contributing to LTA effects in vivo have never been investigated. Using mice deficient for LBP, CD14, TLR2, TLR4, or PAFR, we now examined the role of these molecules in pulmonary inflammation induced by highly purified LTA in vivo. Although pulmonary LBP increased dose-dependently following administration of LTA, the inflammatory response was unaltered in LBP-/- mice. TLR2 proved to be indispensable for the initiation of an inflammatory response, as polymorphonuclear cell influx, TNF-alpha, keratinocyte-derived chemokine, and MIP-2 release were abolished in TLR2-/- mice. Minor effects such as moderately decreased TNF-alpha and MIP-2 levels were observed in the absence of CD14, indicating a role for CD14 as a coreceptor. Quite surprisingly, the absence of TLR4 greatly diminished pulmonary inflammation and the same phenotype was observed in PAFR-/- animals. In contrast to all other mice studied, only TLR4-/- and PAFR-/- mice displayed significantly elevated IL-10 pulmonary concentrations. These data suggest that TLR2 is the single most important receptor signaling the presence of LTA within the lungs in vivo, whereas TLR4 and PAFR may influence lung inflammation induced by LTA either by sensing LTA directly or through recognition and signaling of endogenous mediators induced by the interaction between LTA and TLR2.
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PMID:Lipoteichoic acid-induced lung inflammation depends on TLR2 and the concerted action of TLR4 and the platelet-activating factor receptor. 1829 74

Understanding the changes in host gene expression that occur with bacterial infection will help to elucidate the basis of molecular genetic control of disease resistance. The effect of infecting chicks with Salmonella enterica serovar Enteritidis on the RNA expression level of Toll-like receptor (TLR) genes, and the correlation between TLR RNA expression level and bacterial burden in the cecum and spleen of young birds was studied. Chicks from two advanced intercross lines were either infected or mock infected with S. enteritidis at 1 day of age. The RNA expression levels of TLR2, TLR4 and TLR5 genes were assessed by quantitative reverse transcriptase-PCR (qRT-PCR) in cecum and spleen tissues harvested at one week post-infection. Infected chicks had significant upregulation of TLR2 RNA expression in spleen, TLR4 RNA expression in both cecum and spleen, and downregulation of TLR5 RNA expression in cecum. Bacterial burden of S. enteritidis in infected birds was not correlated with TLR RNA expression level. Infecting chicks with S. enteritidis caused an increase in TLR2, TLR4 and TLR5 RNA expression level in spleen in males but not in females. The effect of sex on response to S. enteritidis infection suggests a role for TLR signaling pathways in sex-based modulation of immune response to pathogens. High correlation between TLR2 and TLR4 mRNA expression level in cecum of S. enteritidis infected birds suggests coordinated regulation or simultaneous stimulation of these genes by S. enteritidis. In conclusion, this study clearly showed that young chicks respond to S. enteritidis infection by upregulating TLR2, TLR4 RNA expression. The downregulation of TLR5 RNA expression was observed in cecum by S. enteritidis infection, which might be beneficial to protect host cells from overstimulation by bacterial flagellin.
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PMID:Toll-like receptor gene expression in cecum and spleen of advanced intercross line chicks infected with Salmonella enterica serovar Enteritidis. 1839 16

Gram-negative bacterial infection is a major cause of sepsis and septic shock. An important inducer of inflammation underlying both syndromes is the cellular recognition of bacterial products through pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). We identified a novel antagonistic mAb (named 1A6) that recognizes the extracellular portion of the TLR4-MD-2 complex. If applied to mice before infection with clinical isolates of Salmonella enterica or Escherichia coli and subsequent antibiotic therapy, 1A6 prevented otherwise fatal shock, whereas application of 1A6 after infection was ineffective. In contrast, coapplication of 1A6 and an anti-TLR2 mAb up to 4 h after infection with Gram-negative bacteria, in combination with the start of antibiotic therapy (mimicking clinical conditions), provided robust protection. Consistent with our findings in mice, dual blockade of TLR2 and TLR4 inhibited TNF-alpha release from human peripheral blood mononuclear cells upon Gram-negative bacterial infection/antibiotic therapy. Both murine splenocytes and human PBMCs released IFN-gamma in a TLR4-dependent manner, leading to enhanced surface TLR2 expression and sensitivity for TLR2 ligands. Our results implicate TLR2 as an important, TLR4-driven sensor of Gram-negative bacterial infection and provide a rationale for blockade of both TLRs, in addition to antibiotic therapy for the treatment of Gram-negative bacterial infection.
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PMID:TLR4-induced IFN-gamma production increases TLR2 sensitivity and drives Gram-negative sepsis in mice. 1864 71

For viral infectious diseases, reliable biomarkers capable of monitoring recovery and therapeutic effects and that simultaneously discriminate between viral and bacterial infection are necessary. In this study, by using flow-cytometric quantification system, Toll-like receptor 2 (TLR2) expression levels on monocytes of influenza patients (n=47) were compared with those of healthy volunteers (n=50). Subsequently, throughout their acute, convalescent and healed phases, TLR2, C-reactive protein (CRP), serum amyroid A (SAA), and neopterin levels were followed. Additionally, TLR2 levels in other viral infectious diseases were assayed. The results showed that TLR2 level in influenza patients was remarkably up-regulated in acute phase compared to healthy volunteers (p<0.001). Thereafter, TLR2 levels normalized in good accordance with their recovery processes. CRP and neopterin levels were relatively widely distributed from normal to abnormally high levels in acute phase in spite of similar disease severity among the patients. SAA levels did not necessarily reflect the patients' clinical course during their recovery. Clinical observations of other viral infections also indicated that TLR2 levels were compatible with infection severity. TLR2 expression level on monocytes might serve as a unique biomarker useful in viral infectious diseases.
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PMID:Toll-like receptor 2 expression level on monocytes in patients with viral infections: monitoring infection severity. 1865 24

Research into intracellular sensing of microbial products is an up and coming field in innate immunity. Toll-like receptors (TLRs) recognize Brucella spp. and bacterial components and initiate mononuclear phagocyte responses that influence both innate and adaptive immunity. Recent studies have revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella infection. TLR2, TLR4 and TLR9 have been implicated in host interactions with Brucella; however, TLR9 has the most prominent role. Further, the relationship between specific Brucella molecules and various signal transduction pathways needs to be better understood. MyD88-dependent and TRIF-independent signaling pathways are involved in Brucella activation of innate immune cells through TLRs. We have recently reported the critical role of MyD88 molecule in dendritic cell maturation and interleukin-12 production during B. abortus infection. This article discusses recent studies on TLR signaling and also highlights the contribution of NOD and type I IFN receptors during Brucella infection. The better understanding of the role by such innate immune receptors in bacterial infection is critical in host-pathogen interactions.
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PMID:The role of innate immune receptors in the control of Brucella abortus infection: toll-like receptors and beyond. 1866 88

The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice deficient in XIAP had a higher bacterial burden 48 h after infection than wild-type littermates, and exhibited substantially decreased survival. XIAP enhanced NF-kappaB activation upon L. monocytogenes infection of activated macrophages, and prolonged phosphorylation of Jun N-terminal kinase (JNK) specifically in response to cytosolic bacteria. Additionally, XIAP promoted maximal production of pro-inflammatory cytokines upon bacterial infection in vitro or in vivo, or in response to combined treatment with NOD2 and TLR2 ligands. Together, our data suggest that XIAP regulates innate immune responses to L. monocytogenes infection by potentiating synergy between Toll-like receptors (TLRs) and Nod-like receptors (NLRs) through activation of JNK- and NF-kappaB-dependent signaling.
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PMID:XIAP regulates cytosol-specific innate immunity to Listeria infection. 1876 21

Mast cells (MCs) are important effector cells in host defense against bacteria. In the course of a bacterial infection, MCs can be activated by various mechanisms, i.e. bacterial toxins, endogenously produced infection-associated peptides or via complement receptors, fimbrial adhesion molecules and toll-like receptors (TLRs). While some of these mechanisms are well established, the effects of TLR2 ligand-driven MC activation are far less understood. Here, we show that murine mature connective tissue-type MCs, but not immature bone marrow-derived cultured mast cells, express significant amounts of full length TLR2 on their surface. Activation by various TLR2 ligands only induces the selective release of cytokines in peritoneum-derived cultured mast cells (PCMCs) with preferential secretion of pro-inflammatory cytokines (IL-6 > IL-17 > IFN-gamma TNF > IL-1 > GM-CSF) upon stimulation with lipoteichoic acid (LTA). This response is much lower in PCMCs stimulated with the TLR2/6 agonist macrophage-activating lipopeptide-2 (MALP-2), which most prominently triggers the release of the immunomodulatory cytokine IL-10. Furthermore, only LTA but not MALP-2 induces prostaglandin D2 secretion which is again restricted to the mature MC phenotype. These findings suggest that TLR2 ligand-mediated activation of mature MCs, i.e. tissue-residing cells, which most likely occurs during infection, can selectively raise a potent inflammatory or anti-inflammatory response, depending on TLRs which are engaged.
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PMID:Murine mast cells secrete a unique profile of cytokines and prostaglandins in response to distinct TLR2 ligands. 1938 14


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