scholarly journals Role ofToll-Like Receptor 4 in Gram-Positive and Gram-Negative Pneumonia inMice

2004 ◽  
Vol 72 (2) ◽  
pp. 788-794 ◽  
Author(s):  
Judith Branger ◽  
Sylvia Knapp ◽  
Sebastiaan Weijer ◽  
Jaklien C. Leemans ◽  
Jennie M. Pater ◽  
...  
Keyword(s):  
Immune Response ◽  
Mutant Mice ◽  
Respiratory Pathogen ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gram Positive ◽  
Gram Negative ◽  
High Level ◽  
Bacterial Outgrowth

ABSTRACT To determine the role of Toll-like receptor 4 (TLR4) in the immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type mice were intranasally infected with either Streptococcus pneumoniae (a common gram-positive respiratory pathogen) or Klebsiella pneumoniae (a common gram-negative respiratory pathogen). In cases of pneumococcal pneumonia, TLR4 mutant mice showed a reduced survival only after infection with low-level bacterial doses, which was associated with a higher bacterial burden in their lungs 48 h postinfection. In Klebsiella pneumonia, TLR4 mutant mice demonstrated a shortened survival after infection with either a low- or a high-level bacterial dose together with an enhanced bacterial outgrowth in their lungs. These data suggest that TLR4 contributes to a protective immune response in both pneumococcal and Klebsiella pneumonia and that its role is more important in respiratory tract infection caused by the latter (gram-negative) pathogen.

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.

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.

B cells facilitate platelet production mediated by cytokines in patients with essential thrombocythaemia

2014 ◽  
Vol 112 (09) ◽  
pp. 537-550 ◽  
Author(s):  
Chuan-Chuan Liu ◽  
Shu-Ching Wang ◽  
Chen-Wei Kao ◽  
Ruey-Kuen Hsieh ◽  
Ming-Chih Chang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Essential Thrombocythaemia ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
B Cell Activating Factor ◽  
High Level ◽  
Megakaryocyte Differentiation

SummaryWe investigated the role of activated B cells in thrombopoiesis through the production of interleukin (IL)-1beta and IL-6 in patients with essential thrombocythaemia. The number of B cells did not differ between essential thrombocythaemia patients, irrespective of the presence of Janus activated kinase-2 V617F mutation or wild type, and age-matched healthy adults. However, the number of IL-1beta/IL- 6-producing B cells was significantly higher in essential thrombocythaemia patients than that in healthy controls. The relatively high level of IL-1beta/IL-6 production by B cells was associated with serum B cell-activating factor and expression of Toll-like receptor 4 on B cells. A high level of B cell-activating factor was present in essential thrombocythaemia patients with both Janus activated kinase-2 genotypes. Incubation with B cell-activating factor enhanced the expression of Toll-like receptor 4 on B cells. IL-1beta and IL-6 production was not stimulated by B cell-activating factor alone; Toll-like receptor 4 was activated by lipopolysaccharide or patients’ sera to produce IL-1beta and IL-6 in B cells. Moreover, essential thrombocythaemia patient B cells facilitated megakaryocyte differentiation when co-cultured with CD34+ haematopoietic stem cells. Antibody neutralisation of IL-1beta and IL-6 attenuated megakaryocyte differentiation. These data suggest that B cells play a crucial role in thrombopoiesis in essential thrombocythaemia patients.

scholarly journals Synergy between 15-lipoxygenase and secreted PLA2promotes inflammation by formation of TLR4 agonists from extracellular vesicles

2020 ◽  
Vol 117 (41) ◽  
pp. 25679-25689 ◽  
Author(s):  
Van Thai Ha ◽  
Duško Lainšček ◽  
Bernd Gesslbauer ◽  
Eva Jarc-Jovičić ◽  
Tuulia Hyötyläinen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Extracellular Vesicles ◽  
Acyl Chain ◽  
Innate Immune ◽  
Sterile Inflammation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Unsaturated Acyl

Damage-associated endogenous molecules induce innate immune response, thus making sterile inflammation medically relevant. Stress-derived extracellular vesicles (stressEVs) released during oxidative stress conditions were previously found to activate Toll-like receptor 4 (TLR4), resulting in expression of a different pattern of immune response proteins in comparison to lipopolysaccharide (LPS), underlying the differences between pathogen-induced and sterile inflammation. Here we report that synergistic activities of 15-lipoxygenase (15-LO) and secreted phospholipase A2(sPLA2) are needed for the formation of TLR4 agonists, which were identified as lysophospholipids (lysoPLs) with oxidized unsaturated acyl chain. Hydroxy, hydroperoxy, and keto products of 2-arachidonoyl-lysoPI oxidation by 15-LO were identified by mass spectrometry (MS), and they activated the same gene pattern as stressEVs. Extracellular PLA2activity was detected in the synovial fluid from rheumatoid arthritis and gout patients. Furthermore, injection of sPLA2promoted K/BxN serum-induced arthritis in mice, whereby ankle swelling was partially TLR4 dependent. Results confirm the role of oxidized lysoPL of stressEVs in sterile inflammation that promotes chronic diseases. Both 15-LO and sPLA2enzymes are induced during inflammation, which opens the opportunity for therapy without compromising innate immunity against pathogens.

scholarly journals Platelet-bound lipopolysaccharide enhances Fc receptor–mediated phagocytosis of IgG-opsonized platelets

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4803-4805 ◽  
Author(s):  
John W. Semple ◽  
Rukhsana Aslam ◽  
Michael Kim ◽  
Edwin R. Speck ◽  
John Freedman
Keyword(s):  
Flow Cytometry ◽  
Toll Like Receptor ◽  
Autoimmune Thrombocytopenia ◽  
Toll Like Receptor 4 ◽  
Platelet Destruction ◽  
Gram Negative ◽  
Synergistic Increase

Abstract Platelets express Toll-like receptor 4 (TLR4), and this has been shown to be responsible for the thrombocytopenia induced by lipopolysaccharide (LPS) administration in vivo. We studied the role of LPS in mediating platelet phagocytosis by THP-1 cells in vitro by flow cytometry. Opsonization of platelets with an IgG monoclonal (W6/32) antibody or with IgG autoantibody-positive sera from patients with autoimmune thrombocytopenia (AITP) significantly enhanced platelet phagocytosis (P < .001). In contrast, platelet phagocytosis did not occur if platelets were bound with only LPS. If, however, the LPS-bound platelets were also opsonized with either W6/32 or autoantibody-positive sera with titers greater than 4, there was a significant and synergistic increase in Fc-dependent platelet phagocytosis (P < .001, P = .003, P = .048, and P = .047). These results suggest that, in the presence of antiplatelet antibodies, bacterial products can significantly alter platelet phagocytosis, and this may have relevance to how Gram-negative infections enhance platelet destruction in some patients with AITP.

scholarly journals Lipoproteins of Gram-Positive Bacteria: Key Players in the Immune Response and Virulence

2016 ◽  
Vol 80 (3) ◽  
pp. 891-903 ◽  
Author(s):  
Minh Thu Nguyen ◽  
Friedrich Götz
Keyword(s):  
Immune Response ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Key Players ◽  
Toll Like Receptor 2 ◽  
Number Of Publications

SUMMARYSince the discovery in 1973 of the first of the bacterial lipoproteins (Lpp) inEscherichia coli, Braun's lipoprotein, the ever-increasing number of publications indicates the importance of these proteins. Bacterial Lpp belong to the class of lipid-anchored proteins that in Gram-negative bacteria are anchored in both the cytoplasmic and outer membranes and in Gram-positive bacteria are anchored only in the cytoplasmic membrane. In contrast to the case for Gram-negative bacteria, in Gram-positive bacteria lipoprotein maturation and processing are not vital. Physiologically, Lpp play an important role in nutrient and ion acquisition, allowing particularly pathogenic species to better survive in the host. Bacterial Lpp are recognized by Toll-like receptor 2 (TLR2) of the innate immune system. The important role of Lpp in Gram-positive bacteria, particularly in the phylumFirmicutes, as key players in the immune response and pathogenicity has emerged only in recent years. In this review, we address the role of Lpp in signaling and modulating the immune response, in inflammation, and in pathogenicity. We also address the potential of Lpp as promising vaccine candidates.

scholarly journals The role of Toll-like receptor 4 polymorphisms in vaccine immune response

2015 ◽  
Vol 16 (1) ◽  
pp. 96-101 ◽  
Author(s):  
P Pellegrino ◽  
F S Falvella ◽  
S Cheli ◽  
C Perrotta ◽  
E Clementi ◽  
...  
Keyword(s):  
Immune Response ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4
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