Understanding How Lipopolysaccharide Impacts CD4 T-Cell Immunity

McAleer, Jeremy P.; Vella, Anthony T.

doi:10.1615/critrevimmunol.v28.i4.20

Cited by 114 publications

(46 citation statements)

References 120 publications

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“…Also, staphylococcal exotoxin and leukocidin possess the capability to activate TLR4 [8]. These are mainly the live proliferating bacterial cells which are easily recognized by the host macrophage TLR4s [9]. Single nucleotide mutations of genes coding TLRs and their receptors are able to hinder the process of pathogen recognition and elimination.…”

Section: Discussionmentioning

confidence: 99%

Genetic factors responsible for long bone fractures non-union

Szczęsny

Olszewski

Zagozda

et al. 2010

Arch Orthop Trauma Surg

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IntroductionApproximately 10–15% of all fractures of long bones heal with delay, prolonged immobilization and repetitive operative interventions. Despite intense investigations, the pathomechanism of impaired healing of skeletal tissue remains unclear. An important role in the pathomechanism of mal-union of close fractures plays subclinically proceeding infections.AimThe question arises whether colonization and proliferation of bacteria in the fracture gap could be related to the mutation of genes for factors regulating local antimicrobial response, such as pathogen recognizing receptors (PRR), cytokines and chemokines.MethodsWe carried out studies in patients with delayed long bone fractures estimating the frequency of mutation of genes crucial for pathogen recognition (TLR2, TLR4 and CD14), and elimination (CRP, IL-6, IL-1ra), as well as wound healing (TGF-β). The molecular milieu regulating healing process (IGF-1, COLL1a, TGF-β, BMP-2, and PDGF) was validated by Western blot analysis of the gap tissue.ResultsMicrobiological investigations showed the presence of viable bacterial strains in 34 out of 108 gaps in patients with non-healing fractures (31.5%) and in 20 out of 122 patients with uneventful healing (16.4%) (P < 0.05). The occurrence of mutated TLR4 1/W but not 2/W gene was significantly higher (P < 0.05) in the non-healing infected than sterile group. In the non-healing infected group 1/W mutated gene frequency was also higher than in healing infected. In the TGF-β codon 10 a significantly higher frequency of mutated homozygote T and heterozygote C/T in the non-healing infected versus non-healing sterile subgroup was observed (P < 0.05). Similar difference was observed in the non-healing infected versus healing infected subgroup (P < 0.05). The CRP (G1059C), IL1ra (genotype 2/2), IL-6 (G176C), CD14 (G-159T), TLR2 (G2259A) and TLR4/2 (Thr399Ile) polymorphisms did not play evident role in the delay of fracture healing.ConclusionsIndividuals bearing the mutant TLR 4 gene 1/W (Asp299Gly) and TGF-β gene codon 10 mutant T and T/C allele may predispose to impaired pathogen recognition and elimination, leading to prolonged pathogen existence in the fracture gaps and healing delays.

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Section: Discussionmentioning

confidence: 99%

Genetic factors responsible for long bone fractures non-union

Szczęsny

Olszewski

Zagozda

et al. 2010

Arch Orthop Trauma Surg

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“…To confirm the reciprocal response of IFN-γ and IL-10 in mice adapted to hypoxia, ApoE−/− mice were acclimated to 10% O 2 for 5 wk and then challenged with lipopolysaccharide (LPS) which can elicit both Th1 and Th2 responses (Fig. 1e) [26]. Even with the shorter exposure time, the IFN-γ level was decreased while IL-10 level was increased either before or after LPS treatment, confirming the cytokine screen data of chronically (22 wk) adapted mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Low ambient oxygen prevents atherosclerosis

Kang

Sung

Amar³

et al. 2016

J Mol Med

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Large population studies have shown that living at higher altitudes, which lowers ambient oxygen exposure, is associated with reduced cardiovascular disease mortality. However, hypoxia has also been reported to promote atherosclerosis by worsening lipid metabolism and inflammation. We sought to address these disparate reports by reducing the ambient oxygen exposure of ApoE−/− mice. We observed that long term adaptation to 10% O2 (equivalent to oxygen content at ~5000 m), compared to 21% O2 (room air at sea level), resulted in a marked decrease in aortic atherosclerosis in ApoE−/− mice. This effect was associated with increased expression of the anti-inflammatory cytokine interleukin-10 (IL-10), known to be anti-atherogenic and regulated by hypoxia-inducible transcription factor-1α (HIF-1α). Supporting these observations, ApoE−/− mice that were deficient in IL-10 (IL10−/− ApoE−/− double knockout) failed to show reduced atherosclerosis in 10% oxygen. Our study reveals a specific mechanism that can help explain the decreased prevalence of ischemic heart disease in populations living at high altitudes and identifies ambient oxygen exposure as a potential factor that could be modulated to alter pathogenesis.

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“…However, it is probable that microbial translocation contributes to this ongoing cytokine overproduction, as microbial molecules, including lipopolysaccharide and other toll-like receptor (TLR) ligands are known to potently stimulate cytokine production by macrophages and other immune system, and nonimmune system, cells. 51,112,113 Additionally, we have seen that exposure of human B cells to TLR ligands (TLR2 ligand) led to the development of a GC-like B cell phenotype, similar to that seen preceding the development of AIDS-NHL. 51,113 …”

Section: Factors That Drive B Cell Activation In Hiv Infectionmentioning

confidence: 81%

Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma

Epeldegui

Martı́nez-Maza

2015

Forum Immun Dis Ther

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HIV infection is associated with a greatly elevated risk for the development of non-Hodgkin lymphoma (NHL), which while diminished, remains elevated in the highly active antiretroviral therapy (HAART) era. Chronic B cell activation, driven by contact with HIV virions, B cell-stimulatory cytokines, viruses (EBV, HPV, HCV), and by high levels of antigenic stimulation occurs in HIV infected persons, and it is seen at even higher levels in those who go on to develop AIDS-NHL. Evidence from multiple studies indicates that elevated serum levels of several B cell-stimulatory cytokines and biomarkers are seen preceding AIDS-NHL, as well as in immunocompetent persons that develop NHL. Phenotypic changes in circulating B cells also are seen preceding AIDS-NHL, including the expression of AICDA, and of cell-surface molecules and miRNA that are associated with activated B cells. HAART only partially normalizes the immune system of treated HIV+ persons as they still show clear evidence for ongoing inflammation and immune activation in, even those who show complete suppression of HIV viremia. Together, this provides ample evidence to support the notion that chronic activation of B cells contributes to the genesis of B cell lymphomas.

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Understanding How Lipopolysaccharide Impacts CD4 T-Cell Immunity

Cited by 114 publications

References 120 publications

Genetic factors responsible for long bone fractures non-union

Genetic factors responsible for long bone fractures non-union

Low ambient oxygen prevents atherosclerosis

Immune Activation: Contribution to AIDS-Associated Non-Hodgkin Lymphoma

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