A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy

Hidaka, Fumiko; Matsuo, Susumu; Muta, Tsuyoshi; Takeshige, Koichiro; Mizukami, Tomoyuki; Nunoi, Hiroyuki

doi:10.1016/j.clim.2006.01.005

Cited by 96 publications

(77 citation statements)

References 42 publications

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“…Broadly, viral nucleic acids (dsRNA, ssRNA, CpG oligodeoxynucleotides) are detected by the endosomal TLRs (3, 7, 8, 9), whereas components of bacteria (peptidoglycans/lipoproteins, lipopolysaccharides) are detected by the cell surface TLRs (2, 4) 3, 4. Recent in vitro and in vivo studies on influenza pathogenesis have shown that TLR activation induces expression of type I interferons and pro‐inflammatory cytokines (e.g., IL‐6, TNF‐α), limiting viral replication and dissemination, mediating tissue inflammation, and link to adaptive immunity development 3, 7, 8, 9, 10, 11, 123, 7, 10, 13.…”

Section: Introductionmentioning

confidence: 99%

Role of human Toll‐like receptors in naturally occurring influenza A infections

Lee

Wong

Hui

et al. 2013

Influenza Resp Viruses

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BackgroundWe investigated the roles of Toll‐like receptors (TLRs) in naturally occurring influenza.MethodsA prospective, case – control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset <48 hours, before treatment) were compared with age‐/gender‐matched controls. TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs – total, myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of RLRs (RIG‐1, MDA‐5) was evaluated using real‐time PCR. Concomitant signaling molecules expression, plasma cytokine/chemokine concentrations, and respiratory tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with TLR‐specific ligands for cytokine responses.ResultsForty two patients with influenza (24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients' mean age was 68 ± 16 years; 81% had respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: −0·46 to −0·69 for TLR9, TLR8, and TLR3; P‐values <0·05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho‐MAPKs, IκB) and inflammatory cytokines (IL‐6, sTNFR‐1, CCL2/MCP‐1; CXCL10/IP‐10, IFN‐γ) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls.ConclusionsOur results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza.

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Section: Introductionmentioning

confidence: 99%

Role of human Toll‐like receptors in naturally occurring influenza A infections

Lee

Wong

Hui

et al. 2013

Influenza Resp Viruses

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“…It also could help in cases of low libido and impotence, especially in the elderly (Destrem, 1956). In a recent study, RJ was reported to contain testosterone and to have steroid hormone-type activities (Hidaka et al, 2006). Moreover, El-Banby (1987) reported that when royal jelly was administered as a 10% solution either intraperitoneally or through a stomach tube to male rats, it stimulated the production of luteinising hormone, testosterone and progesterone.…”

Section: Introductionmentioning

confidence: 99%

Impact of royal jelly to improve reproductive performance of male rabbits under hot summer conditions

El-Hanoun¹,

Elkomy²,

Fares³

et al. 2014

World rabbit sci.

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To alleviate the deleterious effect of heat stress during summer conditions on male rabbits' reproduction, 40 V Line adult rabbit bucks (on av. 8 mo old) were divided into 4 experimental groups and exposed to temperatures ranging from 23 to 36°C. Bucks in the 1 st , 2 nd , 3 rd , and 4 th group were supplemented with 0, 50, 100 or 150 mg of Chinese royal jelly (RJ)/kg twice per week, respectively, over a 20-wk period. Semen quality and blood biochemical constituents were evaluated. RJ at any dose exhibited a significant increase (P<0.05) in rabbits' sperm concentration, total sperm output, sperm motility, live sperm and normal sperm compared to the untreated controls. Plasma total protein, albumin, globulin, glucose and high density lipids (HDL) concentrations were significantly (P<0.05) boosted in the RJ groups compared to the controls. In contrast, RJ treatment resulted in a significant (P<0.05) reduction in plasma total lipids, triglycerides, cholesterol and low density lipids (LDL) concentrations. Treatment with RJ significantly boosted (P<0.05) testosterone concentration in the RJ groups to reach 110, 120 and 128%, respectively, of the control group. Improved kidney and liver functions were observed in the RJ bucks groups where plasma creatinine, urea concentrations, aspartate aminotransferase and alanine aminotransferase enzyme activities were significantly (P<0.05) decreased by RJ treatments. Treating bucks subjected to heat stress by different RJ doses increased (P<0.05) total antioxidant capacity to 106, 111 and 115% of basal, but significantly reduced (P<0.05) malondialdehyde and thiobarbituric acid reactive substances compared to the untreated. It was concluded that Chinese royal jelly supplementation for heat-stressed male rabbits can counteract summer infertility and improve their physiological status.

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“…The role of cell surface sialic acid receptors in the determination of host specificity of influenza viruses is well documented and therefore the genes encoding these receptors and their associated glycan modifications are potential candidates [55][56][57][58]. Cytokine dysregulation has been shown to be a feature of A/H5N1 infection in clinical and animal studies [59][60][61] and various aspects of innate immunity including collectin-like mannose-binding lectin, tolllike receptors (TLR 3,7,8), cytokines, chemokines, and interferon-inducible proteins such as MxA are also plausible candidates [62][63][64][65][66][67][68]. Interestingly, susceptibility to other viral respiratory pathogens has been traced to genes of the innate immune system [69][70][71][72][73].…”

Section: Biological Plausibilitymentioning

confidence: 99%

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

et al. 2010

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SUMMARYThe apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.

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A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy

Cited by 96 publications

References 42 publications

Role of human Toll‐like receptors in naturally occurring influenza A infections

Role of human Toll‐like receptors in naturally occurring influenza A infections

Impact of royal jelly to improve reproductive performance of male rabbits under hot summer conditions

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

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