Regulation of Toll-like Receptor 5 Gene Expression and Function on Mucosal Dendritic Cells

Feng, Ting; Cong, Yingzi; Alexander, Katie L.; Elson, Charles O.

doi:10.1371/journal.pone.0035918

Cited by 25 publications

(25 citation statements)

References 49 publications

(72 reference statements)

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“…TLR5 is abundantly expressed in lung tissues [ 43 , 44 ] and plays an important role in protection against respiratory pathogens, thereby increasing the benefit of flagellin as an effective mucosal adjuvant. The intranasal route of antigen administration mimics natural infection and induces both local and systemic immune responses.…”

Section: Introductionmentioning

confidence: 99%

Protection against Multiple Influenza A Virus Strains Induced by Candidate Recombinant Vaccine Based on Heterologous M2e Peptides Linked to Flagellin

et al. 2015

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Matrix 2 protein ectodomain (M2e) is considered a promising candidate for a broadly protective influenza vaccine. M2e-based vaccines against human influenza A provide only partial protection against avian influenza viruses because of differences in the M2e sequences. In this work, we evaluated the possibility of obtaining equal protection and immune response by using recombinant protein on the basis of flagellin as a carrier of the M2e peptides of human and avian influenza A viruses. Recombinant protein was generated by the fusion of two tandem copies of consensus M2e sequence from human influenza A and two copies of M2e from avian A/H5N1 viruses to flagellin (Flg-2M2eh2M2ek). Intranasal immunisation of Balb/c mice with recombinant protein significantly elicited anti-M2e IgG in serum, IgG and sIgA in BAL. Antibodies induced by the fusion protein Flg-2M2eh2M2ek bound efficiently to synthetic peptides corresponding to the human consensus M2e sequence as well as to the M2e sequence of A/Chicken/Kurgan/05/05 RG (H5N1) and recognised native M2e epitopes exposed on the surface of the MDCK cells infected with A/PR/8/34 (H1N1) and A/Chicken/Kurgan/05/05 RG (H5N1) to an equal degree. Immunisation led to both anti-M2e IgG1 and IgG2a response with IgG1 prevalence. We observed a significant intracellular production of IL-4, but not IFN-γ, by CD4+ T-cells in spleen of mice following immunisation with Flg-2M2eh2M2ek. Immunisation with the Flg-2M2eh2M2ek fusion protein provided similar protection from lethal challenge with human influenza A viruses (H1N1, H3N2) and avian influenza virus (H5N1). Immunised mice experienced significantly less weight loss and decreased lung viral titres compared to control mice. The data obtained show the potential for the development of an M2e-flagellin candidate influenza vaccine with broad spectrum protection against influenza A viruses of various origins.

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Section: Introductionmentioning

confidence: 99%

Protection against Multiple Influenza A Virus Strains Induced by Candidate Recombinant Vaccine Based on Heterologous M2e Peptides Linked to Flagellin

et al. 2015

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“…In a similar manner, TLR5 −/− mice have augmented Foxp3 + Tregs compared to wildtype mice . TLR5 ligation promotes T‐effector cells while opposing Foxp3 + Treg generation in vitro , suggesting that TLR5 signaling affects the Treg/Teff balance.…”

Section: Microbiota Effects On Cd4+ T Cellsmentioning

confidence: 78%

Microbiota activation and regulation of innate and adaptive immunity

Alexander

Targan

Elson

2014

Immunological Reviews

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141

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Summary The human host has co-evolved with the collective of bacteria species, termed microbiota, in a complex fashion that affects both innate and adaptive immunity. Differential regulation of regulatory T-cell and effector T-cell responses are a direct result of specific microbial species present within the gut, and this relationship is subject is dysregulation during inflammation and disease. The microbiota varies widely between individuals and has a profound effect on how one reacts to various environmental stimuli, particularly if a person is genetically predisposed to an immune-mediated inflammatory disorder such as inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Approximately half of all CD patients have elevated antibodies to CBir1, a microbiota flagellin common to mice and humans, demonstrating flagellins as immunodominant antigens in the intestines. This review focuses on the use of flagellins as probes to study microbiota specific responses in the context of health and disease as well as probes of innate and adaptive responses employed by the host to deal with the overwhelming bacterial presence of the microbiota.

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“…Recently, Feng et al . reported reduced expression of Tlr5 in mouse bone‐marrow‐derived dendritic cells in response to a set of TLR ligands, including enteric lipopolysaccharide (TLR4 ligand), CpG ODN (TLR9 ligand) and flagellin (TLR5 ligand). These findings are consistent with our results of reduced Tlr5 expression in response to P. gingivalis .…”

Section: Discussionmentioning

confidence: 99%

Aging and contribution of MyD88 and TRIF to expression of TLR pathway‐associated genes following stimulation with Porphyromonas gingivalis

Shaik‐Dasthagirisaheb

Huang

Weinberg

et al. 2014

J of Periodontal Research

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BACKGROUND AND OBJECTIVE Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease including socioeconomic status, genetics, age, however, inflammation elicited by the presence of specific bacteria in the subgingival space is thought to drive the majority of soft and hard tissue destruction. Porphyromonas gingivalis is closely associated with periodontal disease. Toll-like receptors (TLRs) and their intracellular signaling pathways play roles in host responses to P. gingivalis. The focus of current study was to use microarray analysis to define the contributions that TLR adaptor molecules MyD88 and TRIF, and aging have on TLR pathway associated mRNA expression in response to P. gingivalis. MATERIALS AND METHODS Bone marrow derived macrophages (BMØ) from wild type (Wt), MyD88-KO and TrifLps2 mice at 2-months and 12-months of age were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison to medium alone control. RESULTS Using a two-fold cut-off in mRNA expression criteria, differential expression of 32 genes was observed when Wt BMØ from 2-month old mice were cultured with P. gingivalis compared with medium alone control. When compared with 2-month old Wt, 21 and 12 genes were differentially expressed (P<0.05) as a result of MyD88 or TRIF mutations respectively. The expression of 5 genes was significantly (P<0.05) reduced in the 12-month group compared to the 2-month group in Wt BMØ following culture with P. gingivalis. Age also influenced expression of genes in MyD88-KO and TrifLps2 mice challenged with P. gingivalis. CONCLUSION Our results indicate that P. gingivalis induces differential expression of TLR pathway associated genes, and both MyD88, and TRIF play roles in the expression of these genes. Age also played a role in the expression of TLR-associated genes following stimulation of BMØ with P. gingivalis.

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Regulation of Toll-like Receptor 5 Gene Expression and Function on Mucosal Dendritic Cells

Cited by 25 publications

References 49 publications

Protection against Multiple Influenza A Virus Strains Induced by Candidate Recombinant Vaccine Based on Heterologous M2e Peptides Linked to Flagellin

Protection against Multiple Influenza A Virus Strains Induced by Candidate Recombinant Vaccine Based on Heterologous M2e Peptides Linked to Flagellin

Microbiota activation and regulation of innate and adaptive immunity

Aging and contribution of MyD88 and TRIF to expression of TLR pathway‐associated genes following stimulation with Porphyromonas gingivalis

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