Mucosal interplay among commensal and pathogenic bacteria: Lessons from flagellin and Toll‐like receptor 5

Rumbo, Martı́n; Nempont, Clément; Kraehenbuhl, Jean–Pierre; Sirard, Jean‐Claude

doi:10.1016/j.febslet.2006.04.036

Cited by 66 publications

(56 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TLR5 has been identified as the main pattern recognition receptor required for flagellinmediated immune signalling [17]. TLR5 signalling depends on MyD88 and results in activation of MAPK, nuclear translocation of NF-kB and production of various pro-inflammatory cytokines and chemokines [18]. Moreover, a previous report found that TLR5 cooperates with TLR4, suggesting that TLR4 deficiency will affect flagellin-mediated responses [19].…”

Section: Introductionmentioning

confidence: 99%

“…Hence, in the respiratory tract, bronchial and alveolar epithelial cells with alveolar macrophages are the main sentinels in the detection of microbial signals through innate receptors like the TLRs [33]. A variety of studies have demonstrated that lung and intestinal epithelial cells respond to flagellin by producing PMN-specific chemokines (CXCL1, CXCL5 or CXCL8), cytokines (TNF-a and IL-6) and antimicrobial molecules (NO and h-bD2) [18]. These findings agree with TLR5's predominant expression in lung and intestinal epithelial cells; hence, the epithelium is considered to be one of the main TLR5-responsive compartments [34,35].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

et al. 2009

View full text Add to dashboard Cite

Bacterial products (such as endotoxins and flagellin) trigger innate immune responses through TLRs. Flagellin-induced signalling involves TLR5 and MyD88 and, according to some reports, TLR4. Whereas epithelial and dendritic cells are stimulated by flagellin in vitro, the cell contribution to the in vivo response is still unclear. Here, we studied the respective roles of radioresistant and radiosensitive cells in flagellin-induced airway inflammation in mice. We found that i.n. delivery of flagellin elicits a transient change in respiratory function and an acute, pro-inflammatory response in the lungs, characterized by TLR5-and MyD88-dependent chemokine secretion and neutrophil recruitment. In contrast, TLR4, CD14 and TRIF were not essential for flagellin-mediated responses, indicating that TLR4 does not cooperate with TLR5 in the lungs. Respiratory function, chemokine secretion and airway infiltration by neutrophils were dependent on radioresistant, TLR5-expressing cells. Furthermore, lung haematopoietic cells also responded to flagellin by activating TNF-a production. We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses.Key words: Chemokine . Epithelium . Flagellin . Lung inflammation . TLR5 IntroductionUpon challenge with respiratory pathogens, the airways rapidly develop a pro-inflammatory response initiated by environmental agents including microbe-associated molecular patterns such as Gram-negative bacteria LPS or endotoxins. This proinflammatory reaction plays an important role in the innate defense against respiratory pathogens [1,2]. Physiological changes induced by endotoxin inhalation include pulmonary Ã These authors contributed equally to this work. Eur. J. Immunol. 2009. 39: 1587-1596 DOI 10.1002 Innate immunity 1587 function and bronchoconstriction, cytokine and chemokine production, PMN recruitment, increased permeability of the alveolar epithelium and the associated endothelium [3][4][5][6]. TLR4 [7], together with MD-2, LPS-binding protein and CD14 detect endotoxins and play a critical role in the initiation of the pulmonary response to systemic and mucosal endotoxin administration [5,[8][9][10]. The pulmonary inflammation to endotoxin involves TLR4 signalling in both the parenchyma cells like endothelial and epithelial cells and the haematopoietic cells, i.e. monocytes, dendritic cells and neutrophils [11]. In addition, TLR4 signalling contributes to the development and progression of chronic respiratory disease including asthma [12][13][14][15][16].Flagellin is the major constituent of flagella from Gramnegative and Gram-positive bacteria. TLR5 has been identified as the main pattern recognition receptor required for flagellinmediated immune signalling [17]. TLR5 signalling depends on MyD88 and results in activation of MAPK, nuclear translocation of NF-kB and production of various pro-inflammatory cytokines and chemokines [18]. Moreover, a previous ...

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

et al. 2009

View full text Add to dashboard Cite

show abstract

“…However, TLRs detect specific molecules which are not exclusive to pathogenic organisms. For example, TLR4 recognizes LPS [37], which is present on all Gram-negative bacteria, including non-pathogenic bacteria, and TLR5 [42] recognizes flagellin [43], also expressed by most gut commensal [44]. Various TLR ligands have been shown to modulate the immune response [45][46][47] and act as vaccine adjuvants regardless of their pathogenic or non-pathogenic origin (i.e LPS, CpG DNA).…”

Section: Introductionmentioning

confidence: 99%

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Liu

Wetzler

Massi

2008

Vaccine

View full text Add to dashboard Cite

Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. N. meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluate the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-γ in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.

show abstract

“…We and others have shown that i.v. injection of flagellins promotes a systemic response, characterized by the production of proinflammatory mediators (such as TNF-␣ or IL-6) and DC activation (5,6,(13)(14)(15)(16)(17). Furthermore, flagellins trigger mucosa-specific innate and adaptive defense mechanisms (18 -20).…”

Section: Deletion Of Flagellin's Hypervariable Region Abrogates Antibmentioning

confidence: 99%

“…Bacterial flagellins (the major flagella components in many bacterial pathogens) are specific, unique agonists for TLR5 activation (5,6). The FliC flagellin from Salmonella enterica serovar Typhimurium is the paradigm for studies on flagellum structure-function, immunity, and TLR5 signaling (6 -9).…”

Section: Deletion Of Flagellin's Hypervariable Region Abrogates Antibmentioning

confidence: 99%

Deletion of Flagellin’s Hypervariable Region Abrogates Antibody-Mediated Neutralization and Systemic Activation of TLR5-Dependent Immunity

Nempont

Cayet

Rumbo

et al. 2008

The Journal of Immunology

Self Cite

118

134

View full text Add to dashboard Cite

TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin’s hypervariable region abrogated the protein’s intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.

show abstract

Mucosal interplay among commensal and pathogenic bacteria: Lessons from flagellin and Toll‐like receptor 5

Cited by 66 publications

References 90 publications

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Deletion of Flagellin’s Hypervariable Region Abrogates Antibody-Mediated Neutralization and Systemic Activation of TLR5-Dependent Immunity

Contact Info

Product

Resources

About