Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general "rheostat" that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis ...

Sepsis is the leading cause of death in intensive care units, which reflects detrimental host response to infection where lipopolysaccharide (LPS) shared by Gram-negative bacteria acts as a potent activator of immune cells via Toll-like receptor 4 (TLR4). Recently it was found that TLR4 downstream signalling leads to the accumulation ...

It is becoming increasingly clear that innate immune mediators play a role in regulating adaptive immune responses in asthma pathogenesis. Cockroach exposure is a major risk factor for the development of asthma. In this study we asked whether German cockroach (GC) feces (frass) could initiate an innate immune response. Naive ...

We have recently demonstrated that oxidants can activate monocytes via an action on Toll-like receptor (TLR) 2; however, it is unclear what functional consequence this has on immune surveillance for Gram-negative and -positive bacteria. Gram-negative and -positive bacteria and their related pathogen-associated molecular patterns (PAMPs) are sensed by TLR4 and ...

In this study, 2-Cys Plasmodium berghei ANKA (PbA) peroxiredoxin (Prx) was identified as an antigenic protein recognized by an anti-PbA IgE antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. Innate immune responses to PbAPrx were examined using cells from mice deficient in Toll-like receptors (TLR) or related molecules, and ...

Mycobacterium avium (MAV) and M. abscessus (MAB) are ubiquitous environmental organisms increasingly recognized to cause chronic lung disease in patients with apparently normal immune function. Little is yet known about their human pathophysiology. Our objective was to examine cytokine and chemokine responses (protein and gene expression) and signaling pathways triggered ...

Gene delivery applications to treat lung diseases are, in some instances, suboptimal due to deleterious host inflammatory reactions. Current DNA plasmids (pDNA) exert toxicity in part via unmethylated CpG motifs that stimulate Toll-like receptor (TLR)9-expressing leukocytes; however, the airway epithelial response has not been well defined. Bronchial epithelial cells (BEAS-2B) ...

Marsupials are born in a relatively underdeveloped state and develop during a period of intensive maturation in the postnatal period. During this period, the young marsupial lacks a competent immune system, but manages to survive despite the potential of exposure to environmental pathogens. Passive immune transfer via the milk is ...

BACKGROUND: Toll-like receptors (TLR) 2 and TLR4 expressed on innate immune cells are important mediators of the immune response to pathogens. In this study, we hypothesized that burn injury results in altered cytokine secretion profiles after TLR2 or TLR4 ligation that is associated with altered TLR expression on innate immune ...

OBJECTIVE: Examination of the interaction between gram-positive bacterial superantigens and toll-like receptor 2 (TLR2) in health and critical illness. DESIGN: Laboratory ex vivo model and prospective clinical, cohort study. SETTING: Two research laboratories in university hospitals and two intensive care units. SUBJECTS/PATIENTS: Laboratory study was performed in transfected HeLa cells ...

Mycobacterium abscessus (Mab) is an emerging and rapidly growing non-tuberculous mycobacterium (NTM). Compared with M. tuberculosis, which is responsible for tuberculosis, much less is known about NTM-induced innate immune mechanisms. Here we investigated the involvement of pattern-recognition receptors and associated signalling in Mab-mediated innate immune responses. Mab activated the extracellular ...

Hog confinement workers are at high risk to develop chronic bronchitis as a result of their exposure to organic dust. Chronic bronchitis is characterized by inflammatory changes of the airway epithelium. A key mediator in inflammation is Toll-like receptor 2 (TLR2). We investigated the role of TLR2 in pulmonary inflammation ...

Macrophage migration inhibitory factor (MIF) plays vital roles in the regulation of responses to stimuli acting via Toll-like receptor (TLR)-4. Recently, a specific small molecule inhibitor of MIF (ISO-1) has been described. We investigated the effects of ISO-1 on TLR responses in primary human monocytes and monocyte-derived macrophages (MDM). In ...

Topical lithium (Li) gluconate has a beneficial effect on seborrhoeic dermatitis (SD), unlike oral lithium (Li) used in psychiatry. SD is an inflammatory dermatitis associated, in most of cases, with colonization by lipophilic yeasts of the genus Malassezia. However, the exact mechanism of action of Li gluconate in SD still ...

The stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of critical proinflammatory cytokines that are necessary to activate potent immune responses. LPS/TLR4 signaling has been intensively studied in the past few years. Here we review molecules involved in TLR4-mediated signaling, including players that are involved in ...

Odontoblasts and fibroblasts are suspected to influence the innate immune response triggered in the dental pulp by micro-organisms that progressively invade the human tooth during the caries process. To determine whether they differ in their responses to oral pathogens, we performed a systematic comparative analysis of odontoblast-like cell and pulp ...

Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell ...

Toll-like receptors play an important role in innate and adaptive immunity and in balancing immune responses with tolerance. TLR2 is related to protection against allergies and allergic asthma by sensing pathogen associated patterns as lipoproteins and lipopeptides. A constant Th1 triggering is thought to prevent Th2 related disorders.TLR2 is expressed ...

Crohn's disease (CD) is a chronic intestinal inflammatory pathology, which develops as a result of innate immune signals, such as the activation of Toll-like receptors (TLRs), and adaptive immune signals, including Th1 cytokine release. We have recently demonstrated in TNBS-induced colitis, a murine model of CD, that VIP plays a ...

Serum amyloid A (SAA), a classical acute-phase protein, is produced predominantly by hepatocytes in response to injury, infection, and inflammation. It has been shown that SAA primes leukocytes and induces the expression and release of proinflammatory cytokines. Here, we report that SAA induces NO production by murine peritoneal macrophages. Using ...

The sulfated polysaccharide carrageenan (CGN) induces activation of NFkappaB and interleukin 8 (IL-8) in human colonic epithelial cells through a pathway of innate immunity mediated by Bcl10 (B-cell CLL/lymphoma 10). In this report, we identify Toll-like receptor 4 (TLR4), a member of the family of innate immune receptors, as the ...

Garlic has long been used as a folk medicine. Numerous studies have demonstrated that a garlic extract and its sulfur-containing compounds inhibited nuclear factor kappa B (NF-kappaB) activation induced by various receptor agonists including lipopolysaccharide (LPS). Toll-like receptors (TLRs) play a key role in sensing diverse microbial products and inducing ...

The antimicrobial peptide LL-37 is generated from skin keratinocytes during infection of Gram-negative bacteria and exerts a microbicidal effect. LL-37 also causes functional changes in mast cells. Mast cells in the skin are involved in the innate immune system response against microbial infections via Toll-like receptors (TLRs), such as TLR4, ...

Modification of cytokine production by gender hormones has been postulated to affect disease susceptibility and outcome. Here we investigate the effect of gender and the menstrual cycle on production of cytokines. Mononuclear cells were isolated every week for 10 consecutive weeks from healthy pre-menopausal women and men. TNF and IL-10 ...

Acute cigarette smoke exposure of the airways (two cigarettes twice daily for three days) induces acute inflammation in mice. In this study, we show that airway inflammation is dependent on Toll-like receptor 4 and IL-1R1 signaling. Cigarette smoke induced a significant recruitment of neutrophils in the bronchoalveolar space and pulmonary ...

The lipid A of LPS activates TLR4 through an interaction with myeloid differentiation protein-2 (MD-2) and the degree of lipid A acylation affects TLR4 responsiveness. Two TLR4 single nucleotide polymorphisms (Asp299Gly and Thr399Ile) have been associated with LPS hyporesponsiveness. We hypothesized that the combination of hypoacylation and these single nucleotide ...

Toll-like receptors (TLRs) are key components of the innate immune system that detect microbial infection and trigger antimicrobial host responses. To determine the role of TLR2 in the expression of pro- and anti-inflammatory cytokines in corneal fibroblasts challenged by fungi, we used siRNA specific for TLR2 to knockdown TLR2 expression ...

Pneumolysin is a pore-forming cytolysin known as a major virulence determinant of Streptococcus pneumoniae. This protein toxin has also been shown to activate the Toll-like receptor 4 (TLR4) signaling pathway. In this study, a mutant S. pneumoniae strain deficient in pneumolysin (Deltaply) and a recombinant pneumolysin protein (rPLY) were constructed. ...

Toll-like Receptors (TLRs) are innate immune receptors that recognize both bacterial and viral pathogens. As the cornea may become infected by these pathogens, leading to vision loss, initial studies addressed the functional presence of TLRs within this tissue, thereby yielding a model of how immunological responses are initiated within the ...

The chemokine CCL20 is crucial for the development of the inflammatory response in the disease COPD. The alveolar epithelium is an important source of CCL20 after stimulation from particulate matter and bacteria. This process contributes to lymphocyte and dendritic cell activation, which is the link between innate and adaptive immunity, ...

Eukaryotic and prokaryotic chaperonin 60s (Cpn60s) activate macrophages to produce pro-inflammatory cytokines. CD14 and TLR4 have been proposed as potential Cpn receptors. In addition, Cpn60s can block LPS-induced activation. This is a dose-related effect, low concentrations block, and high concentrations activate. This may relate to the ability of Cpn60s to ...

Schistosomes carry lipid moieties that interact with the immune system. To understand the consequence of interactions in terms of polarizing the cytokine profiles, the effect of two Toll-like receptor-2 (TLR2) activating schistosomal lipid fractions was studied on whole blood from Gabonese children living in a schistosomiasis endemic area. One fraction ...

Histoplasma capsulatum is a common cause of fungal infection in certain geographic areas, and although most infections are asymptomatic, it is capable of causing histoplasmosis, a disseminated, life-threatening disease, especially in immunocompromised individuals. A deeper understanding of this host-pathogen interaction is needed to develop novel therapeutic strategies to counter lethal ...

BACKGROUND: All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human beta-defensin 2 is the most potent molecule and is inducible by ...

Innate immune responses are essential for controlling poxvirus infection. The threat of a bioterrorist attack using Variola major, the smallpox virus, or zoonotic transmission of other poxviruses has renewed interest in understanding interactions between these viruses and their hosts. We recently determined that TLR3 regulates a detrimental innate immune response ...

BACKGROUND: Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei. Overall mortality approaches 40% yet little is known about mechanisms of host defense. Toll-like receptors (TLRs) are host transmembrane receptors that recognize conserved pathogen molecular patterns ...

BACKGROUND: Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere ...

Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. Few studies have been devoted to address the impact of TLR2 (a fully MyD88-dependent receptor) and TLR3 (a fully TRIF-dependent receptor) co-activation on DC functions, especially ...

Alternative activation of macrophages (Mphi) during helminth infection is a characteristic feature of the host immune response. Alternatively activated macrophages (AAMphi) are distinguished from others by high arginase 1 (Arg-1) activity, low nitric oxide (NO), and high interleukin 10 (IL-10) production. In murine models, these cells have been shown to ...

Microglial cells respond to the herpes simplex virus (HSV)-1 by producing proinflammatory cytokines and chemokines. After this inflammatory burst, these cells undergo apoptotic cell death. We have recently demonstrated that both virus-induced immune mediator production and apoptosis were induced through Toll-like receptor 2 (TLR2) signaling. Based upon these findings, we ...

Toll-like receptors (TLRs) play an important role in mediating the down stream signaling of immune response in tuberculosis. The predominance of Th1 response in tuberculous pleurisy prompted us to study the expression profiles of TLR2 and TLR4 on different immune cells and on subsets of T cells obtained from the ...

TLR are primary triggers of the innate immune system by recognizing various microorganisms through conserved pathogen-associated molecular patterns. TLR2 is the receptor for a functional recognition of bacterial lipopeptides (LP) and is up-regulated during various disorders such as chronic obstructive pulmonary disease and sepsis. This receptor is unique in its ...

Toll-like receptors (TLRs) response is critical in innate resistance to infection. Alcohol consumption has been shown to suppress the inflammatory response mediated through TLR4, down regulating the production of inflammatory cytokines. We recently reported that low concentrations of ethanol activate TLR4 signaling in astrocytes and triggers neuroinflammation. Because macrophages are ...

Mammalian TLRs are central mediators of the innate immune system that instruct cells of the innate and adaptive response to clear microbial infections. Here, we demonstrate that human epithelial TLR4 directly protected the oral mucosa from fungal infection via a process mediated by polymorphonuclear leukocytes (PMNs). In an in vitro ...

The PMT gene family in Candida albicans encodes five isoforms of the protein mannosyltransferases that initiate O-mannosylation of secretory proteins. Mutations at the Pmt level have been associated with differences in pathogenicity, e.g. in contrast to pmt5/pmt5, pmt2/PMT2 mutants showed poor virulence. Our objective was to determine whether these differences ...

Uncontrolled TLR4 signaling may induce excessive production of proinflammatory cytokines and lead to harmful inflammation; therefore, negative regulation of TLR4 signaling attracts much attention now. PECAM-1, a member of Ig-ITIM family, can mediate inhibitory signals in T cells and B cells. However, the role and the mechanisms of PECAM-1 in ...

Bacterial lipoproteins (LP) are a family of cell wall components found in a wide variety of bacteria. In this study, we characterized the response of HUCL, a telomerase-immortalized human corneal epithelial cell (HCEC) line, to LP isolated from Staphylococcus (S) aureus. S. aureus LP (saLP) prepared by Triton X-114 extraction ...

BACKGROUND: Despite high bacterial colonization, acute infections are rare in the oral mucosa, implicating tolerogenic predominance. Bacterial antigens like LPSs are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4), associated with LPS receptor (CD14). OBJECTIVES: Toll-like receptor 4 agonist monosphoryl lipid A has been successfully used as ...

To study the immune responses of porcine intestinal epithelial cells to gram-negative bacteria via toll-like receptors (TLRs), originally established porcine intestinal epitheliocyte (PIE) cells were treated with lipopolysaccharide (LPS) or swine-specific enterotoxigenic Escherichia coli (ETEC). Real-time quantitative PCR revealed that PIE cells expressed TLR1-9 and MD-2 mRNAs, preferentially expressed TLR4/MD-2. ...

Small fragments of the extracellular matrix component hyaluronic acid (sHA) are typically produced at sites of inflammation and tissue injury and have been shown to be associated with tumor invasiveness and metastasis. Here we report that exposure of human melanoma cells to sHA leads to nuclear factor kB (NFk-B) activation ...