scholarly journals Toll-like receptor 4 is not required for the full maturation of dendritic cells or for the degradation of Gram-negative bacteria

2002 ◽  
Vol 32 (10) ◽  
pp. 2800-2806 ◽  
Author(s):  
Maria Rescigno ◽  
Matteo Urbano ◽  
Monica Rimoldi ◽  
Barbara Valzasina ◽  
Gianluca Rotta ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Negative

scholarly journals Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria

2008 ◽  
Vol 15 (10) ◽  
pp. 1523-1528 ◽  
Author(s):  
Indreshpal Kaur ◽  
Elizabeth R. Simons ◽  
Asha S. Kapadia ◽  
C. Mark Ott ◽  
Duane L. Pierson
Keyword(s):  
Space Shuttle ◽  
Space Station ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Negative ◽  
Time Points ◽  
Control Subjects ◽  
Intracellular Cytokines ◽  
Blood Specimens

ABSTRACT Astronauts live and work in relatively crowded, confined environments on the Space Shuttle and the International Space Station. They experience a unique set of stressors that contribute to a diminishment of many immune responses. This study investigated the ability of the shuttle crew members' monocytes to respond to gram-negative endotoxin that they could encounter during infections. Blood specimens were collected from 20 crew members and 15 control subjects 10 days before launch, 3 to 4 h after landing, and 15 days after landing and from crew members during their annual medical examination at 6 to 12 months after landing. When challenged with gram-negative endotoxin, the crew member's monocytes collected at all three time points produced lower levels of interleukin-6 (IL-6) and IL-1β and higher levels of IL-1ra and IL-8 compared to those of control subjects. Cytokines were assessed by measuring the number of cells positive for intracellular cytokines. These values returned to normal 6 to 12 months after landing, except for IL-1ra, which was still higher (five- to sixfold) than in controls. This phenomenon was accompanied by an increased expression of Toll-like receptor 4 and decreased expression of CD14 on the crew members' monocytes at all time points. There were also increased levels of the lipopolysaccharide binding protein in the plasma of the crew members 3 to 4 h and 15 days after landing. This study shows that spaceflight-associated factors (in-flight and preflight) modulate the response of monocytes to gram-negative endotoxins.

Increased Expressions of Toll-Like Receptor 4 on Platelet Are Related to Type of Bacteria and Disease Severity in Patients with Sepsis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5365-5365
Author(s):  
Liping Ma ◽  
Xiu-Ju Wang ◽  
Da-Nian Nie ◽  
Yi-Qing Li ◽  
Shuang-Fen Xie ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Inflammatory Cells ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Microbial Infection ◽  
Toll Like Receptor 4 ◽  
Gram Positive ◽  
Severe Problem ◽  
Gram Negative ◽  
Gram Positive Bacteria

Abstract Early diagnosis and treatment of patients with sepsis remain a common and severe problem, especially in leukopenic patients.. Toll-like receptor-4 (TLR4) plays a crucial role in immunity as the first defenses system against microbial infection through binding gram-negative bacterial LPS. Blood platelets are not only involved in hemostasis, they also have many features of classic inflammatory cells. The expression of TLR4 on platelet in patients with sepsis, including gram-positive bacteria and gram-negative bacteria, is not known. Studying the differences between them, we investigated whether the expressions of TLR4 on platelet were associated with platelet activation, serum TNF-a and endotoxin levels in patients with sepsis, 8 patients of them with gram-positive bacteria and 15 patients of them with gram-negative bacteria. The number of platelet and function of coagulation were normal before infecting. Comparing with the heath subjects, the expressions of TLR4 and P-selectin on platelets, the levels of serum TNF-a and endotoxin were higher (P<0.05),and there was a positive correlation was observed between TLR4 and P-selectin, TNF-a, endotoxin respectively, among the gram-negative bacterial subjects. The phenomena were not found among the gram-positive bacterial subjects. In addition, among the gram-negative bacterial subjects, the expression of TLR4 was higher in patients with decreased number of platelets than with normal number of platelets. These results suggest that increased TLR4 on platelet might be an important early sign of gram-negative bacteria in patient with sepsis, it contributes to platelet activating, the inflammatory process and disease activity in infecting host. Above has be doing in more patients with positive blood bacteria culture in our Lab.

scholarly journals Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria

2005 ◽  
Vol 73 (1) ◽  
pp. 532-545 ◽  
Author(s):  
Jill R. Schurr ◽  
Erana Young ◽  
Pat Byrne ◽  
Chad Steele ◽  
Judd E. Shellito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adaptor Protein ◽  
Mouse Strains ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Gram Negative ◽  
Experimental Pneumonia

ABSTRACT Toll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection of Klebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.

scholarly journals Toll-Like Receptor 4 Promotes NO Synthesis by Upregulating GCHI Expression under Oxidative Stress Conditions in Sheep Monocytes/Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shoulong Deng ◽  
Kun Yu ◽  
Baolu Zhang ◽  
Yuchang Yao ◽  
Zhixian Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Negative ◽  
Transgenic Sheep ◽  
And Oxidative Stress

Many groups of Gram-negative bacteria cause diseases that are harmful to sheep. Toll-like receptor 4 (TLR4), which is critical for detecting Gram-negative bacteria by the innate immune system, is activated by lipopolysaccharide (LPS) to initiate inflammatory responses and oxidative stress. Oxidation intermediates are essential activators of oxidative stress, as low levels of free radicals form a stressful oxidative environment that can clear invading pathogens. NO is an oxidation intermediate and its generation is regulated by nitric oxide synthase (iNOS). Guanosine triphosphate cyclohydrolase (GCHI) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, which is essential for the production of inducible iNOS. Previously, we made vectors to overexpress the sheepTLR4gene. Herein, first generation (G1) of transgenic sheep was stimulated with LPSin vivoandin vitro, and oxidative stress and GCHI expression were investigated. Oxidative injury caused by TLR4 overexpression was tightly regulated in tissues. However, the transgenic (Tg) group still secreted nitric oxide (NO) when an iNOS inhibitor was added. Furthermore, GCHI expression remained upregulated in both serum and monocytes/macrophages. Thus, overexpression of TLR4 in transgenic sheep might accelerate the clearance of invading microbes through NO generation following LPS stimulation. Additionally, TLR4 overexpression also enhances GCHI activation.

scholarly journals Higher levels of grp78 and lower levels of tlr4 anticipate a positive evolution of sepsis and patient survival

2017 ◽  
Author(s):  
Razvan C. Stan ◽  
Camila P. Bonin ◽  
Rose Porto ◽  
Francisco G. Soriano ◽  
Maristela M. de Camargo
Keyword(s):  
Patient Survival ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Intensive Care Admission ◽  
Gram Negative ◽  
Downstream Signaling ◽  
Survivor Group ◽  
Positive Evolution ◽  
Glucose Regulated Protein

AbstractIn sepsis caused by Gram-negative bacteria, modulation of Toll-like receptor 4 (TLR4) activity by modulators such as glucose-regulated protein 78 kDa (GRP78), is believed to shift the equilibrium between pro- and anti-inflammatory downstream signaling cascade. We measured daily mRNA tlr4 and grp78 expression levels in peripheral blood of a cohort of septic patients, upon intensive care admission, and modeled these mRNA values based on a sine damping function. We obtained negative correlations between tlr4 and grp78 mRNA in the survivor group. In contrast, such relation is lost in the deceased patients. Loss of homeostasis predicted by our model within the initial 5 days of hospitalization was confirmed by death of those patients up to 28 days later. Measuring the correlation patterns of the expression of these two genes serves as a robust means to gauge sepsis progression, requiring only three points of measurement on the first day of hospitalization.

scholarly journals Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine

2016 ◽  
Vol 82 (14) ◽  
pp. 4264-4278 ◽  
Author(s):  
Stephen R. Coats ◽  
Ahmed Hashim ◽  
Nikolay A. Paramonov ◽  
Thao T. To ◽  
Michael A. Curtis ◽  
...  
Keyword(s):  
Dietary Habits ◽  
Significant Proportion ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Microbial Composition ◽  
Toll Like Receptor 4 ◽  
Gram Negative ◽  
Content Type ◽  
Naturally Occurring ◽  
Intestinal Immune System

ABSTRACTIntestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurringBacteroidetessp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potentEnterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities.IMPORTANCEThe guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders.

scholarly journals Toll-Like Receptor 4 Protects Against Clostridium perfringens Infection in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Masaya Takehara ◽  
Keiko Kobayashi ◽  
Masahiro Nagahama
Keyword(s):  
Clostridium Perfringens ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Positive ◽  
Gram Negative ◽  
Tlr4 Agonist ◽  
Innate Ability ◽  
Recognition Receptor

Toll-like receptor 4 (TLR4) has been reported to protect against Gram-negative bacteria by acting as a pathogen recognition receptor that senses mainly lipopolysaccharide (LPS) from Gram-negative bacteria. However, the role of TLR4 in Gram-positive bacterial infection is less well understood. Clostridium perfringens type A is a Gram-positive bacterium that causes gas gangrene characterized by severe myonecrosis. It was previously demonstrated that C. perfringens θ-toxin is a TLR4 agonist, but the role of TLR4 in C. perfringens infection is unclear. Here, TLR4-defective C3H/HeJ mice infected with C. perfringens showed a remarkable decrease in survival rate, an increase in viable bacterial counts, and accelerated destruction of myofibrils at the infection site compared with wild-type C3H/HeN mice. These results demonstrate that TLR4 plays an important role in the elimination of C. perfringens. Remarkable increases in levels of inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), were observed in C. perfringens-infected C3H/HeN mice, whereas the increases were limited in C3H/HeJ mice. Generally, increased G-CSF accelerates granulopoiesis in the bone marrow and the spleen to exacerbate neutrophil production, resulting in elimination of bacteria. The number of neutrophils in the spleen was increased in C. perfringens-infected C3H/HeN mice compared with non-infected mice, while the increase was lower in C. perfringens-infected C3H/HeJ mice. Furthermore, DNA microarray analysis revealed that the mutation in TLR4 partially affects host gene expression during C. perfringens infection. Together, our results illustrate that TLR4 is crucial for the innate ability to eliminate C. perfringens.

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