FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Cummings, Lisa A.; Barrett, Sara L. Rassoulian; Wilkerson, W. David; Fellnerova, Ivana; Cookson, Brad T.

doi:10.4049/jimmunol.174.12.7929

Cited by 74 publications

(72 citation statements)

References 82 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considerable knowledge has been gained regarding the ability of bacterial flagellin to activate the host immune response, both by signaling through TLR5 and Ipaf and through the generation of adaptive immunity [7,8,11,12,17,29]. Herein we establish that the two flagellin proteins, FliC and FljB, purified from Salmonella possess a similar ability to activate the proinflammatory transcription factor NF-κB.…”

Section: Discussionmentioning

confidence: 78%

Activation of NF-κB-dependent gene expression by Salmonella flagellins FliC and FljB

Simon

Samuel

2007

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Bacterial flagellin is recognized by Toll-like receptor (TLR5) and activates NF-κB which leads to the induction of proinflammatory gene expression. Salmonella expresses two flagellin proteins, FliC and FljB. We purified FliC and FljB and examined the ability of the Salmonella flagellins to activate the NF-κB transcription factor in human embryonic kidney cells. We found that FliC and FljB as purified proteins possessed a comparable specific activity for activation of NF-κB-dependent gene expression in HEK293 cells. We also determined the ability of UV-inactivated bacteria, both wildtype and fliC and fljB mutant strains, to activate NF-κB. Wild-type fliC + /fljB + Salmonella and the fliC + /fljB − mutant strain were robust activators, whereas the fliC − /fljB + and flhC − mutant strains were very poor activators. The NF-κB activation capacity of bacterial strains correlated with their flagellin expression level. Finally, Salmonella cell wall-associated polymeric flagellin displayed greatly reduced ability to activate NF-κB compared to purified monomeric flagellin.

show abstract

Section: Discussionmentioning

confidence: 78%

Activation of NF-κB-dependent gene expression by Salmonella flagellins FliC and FljB

Simon

Samuel

2007

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…Since S. Typhimurium induces caspase-1-dependent apoptosis of dendritic cells via the SPI-1 T3SS, these cells may sense cytosolic flagellin translocation by Salmonella and trigger proinflammatory responses (34). The Peyer's patches of the ileum and the lamina propria would appear to be the most likely anatomical site for sensing of cytosolic flagellin since S. Typhimurium represses flagellin expression at systemic sites such as the mesenteric lymph nodes and spleen (35,36).…”

Section: Discussionmentioning

confidence: 99%

Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium

Sun¹,

Rolán²,

Tsolis³

2007

Journal of Biological Chemistry

154

156

View full text Add to dashboard Cite

Bacterial flagella are filamentous appendages on the cell surface that mediate bacterial motility. The filament of the flagellum is composed of ϳ20,000 flagellin subunits (1). Flagellin monomers of many bacterial species function as pathogen-associated molecular patterns and can be detected by host cells using both surface-localized toll-like receptor 5 (TLR5) 2 and cytosolic Nod-like receptors (2-6). The interaction of flagellin with TLR5 at the cell surface has been characterized in detail, identifying the structural basis for the TLR5-flagellin interaction (7,8). TLR5 sensing has been shown to be important in Legionnaires disease, a respiratory tract infection caused by the bacterium Legionella pneumophila, since human TLR5 polymorphisms correlated with disease susceptibility (7,8). In the intestine, TLR5 localizes to the basolateral surface of enterocytes and to CD11c ϩ lamina propria dendritic cells (9, 10). In these locations, TLR5 is thought to be involved in sensing a breach of the intestinal mucosa by enteroinvasive pathogens, triggering an inflammatory response that limits systemic spread of the bacteria (11).In addition to sensing by TLRs, flagellin was recently shown to be sensed by two different Nod-like receptors, Ipaf and Birc1e (also known as Naip5) (2, 4 -6, 12). Ipaf transmits a proinflammatory signal in response to flagellin by activating the inflammasome, resulting in caspase 1-dependent activation of Il-1␤, which is accompanied by cell death (pyroptosis) (13-17). Birc1e/Naip5 signals in response to flagellin, restricting intracellular growth of L. pneumophila by antagonizing the ability of the bacterium to avoid fusion with lysosomes and form a replicative phagosome (18). Several lines of evidence suggest that pathogens residing in a membrane-bound compartment of the cell, such as L. pneumophila and S. Typhimurium (Salmonella enterica serotype Typhimurium), may release flagellins from their vacuole into the host cytosol, which triggers signaling via Ipaf and Birc1e. First, S. Typhimurium and L. pneumophila mutants lacking flagellin elicit reduced caspase activation, IL-1␤ secretion, and cytotoxicity in macrophages (2, 4 -6, 19). Second, mutants of S. Typhimurium lacking the SPI-1 T3SS and L. pneumophila mutants lacking a functional Type IV secretion system (T4SS) fail to trigger Ipaf-dependent signaling (4,5,19). Third, introduction of purified flagellins into the cytosol of macrophages using pore-forming toxins or detergents or by heterologous expression in Escherichia coli expressing listeriolysin O triggers caspase-1 activation and IL-1␤ activation by an Ipaf-dependent mechanism (2, 4 -6, 20).Although injection of effector proteins into host cells by the S. Typhimurium SPI-1 T3SS has been visualized microscopically (21, 22), it has not yet been demonstrated that in infected cells, bacteria are able to translocate flagellin from a membrane-bound compartment into the cytosol. In this report, we show that S. Typhimurium translocates flagellin into the cytosol of infected cells by a process t...

show abstract

“…[23] When there are huge numbers of CD4 + T cells in the bone marrow, this is anomalous and indicates infection. These cells also play a role in the elimination of intracellular pathogens such as S. typhi, [24] with flagellin (H antigen) of Salmonella being a specific target. [10] The doses used in our study (10 9 cells/ml) had a modulated immune response.…”

Section: Resultsmentioning

confidence: 99%

Splenectomy and Salmonella Typhi Exposure Lead to Quantitative Alterations of Bone Marrow B220+ Cells and CD4+ T Cells on BALB/c Mice

Rifa’i¹

2013

Turk J Immunol

View full text Add to dashboard Cite

Amaç: Bu çalışmada splenektomi yapılan ve Salmonella typhi'ye (S. typhi) maruz bırakılan BALB/c farelerde kemik iliği B220 + hücreleri ve CD4 + T hücrelerinin rölatif yoğunluğundaki kantitatif değişiklikler incelendi. Gereç ve yöntemler:Ketamin anestezisi altında splenektomi yapıldı (65 mg/kg BW). Splenektomiden iki hafta sonra akut doz enjeksiyonu ile S. typhi maruziyeti yapıldı (10 9 hücre/mL) ve doz, ilk dozdan iki hafta sonra tekrarlandı. Kemik iliği B220 + hücreleri ve CD4 + T hücrelerinin rölatif yoğunluğu, BD FACSCalibur™ akım sitometri ile belirlendi. İki yönlü ANOVA ve Tukey HSD testi ile istatistiksel analiz yapıldı. P<0.05 değerleri anlamlı kabul edildi. Bulgular:Tedavilerinin tümü, gözlenen değişkenler üzerinde anlamlı etkilere sahipti. Splenektomi,B220+ hücrelerin oranınını splenektomi yapılmayan farelerdeki %17.34 oranından %5.51'e anlamlı olarak düşürdü. Salmonella typhi maruziyeti tek başına B220 + hücrelerinin rölatif yoğunluğunu anlamlı düzeyde değiştir-medi (%17.92). Splenektomi yapılması ve S.typhi ile karşılaşma B220+ hücreleri %5.9'a düşürdü. CD4 + T hücreleri tüm tedavilere karşı farklı yanıtlar verdi. Kontrollere kıyasla (%0.28), splenektomi CD4 + T hücrelerinin rölatif yoğunluğunu anlamlı düzeyde %0.43'e kadar artırdı. Salmonella typhi maruziyeti tek başına ve splenektomi ile birlikte, CD4 + T hücrelerinin rölatif yoğunluğunu sırası ile %0.55 ve %0.50'ye kadar anlamlı düzeyde artırdı.Sonuç: Bu bulgular, S. typhi maruziyetine kıyasla, splenektominin B220 + hücrelerinin rölatif yoğunluğunu etkileyen başlıca etmen olup, S. typhi maruziyeti CD4 + T hücrelerinin rölatif yoğunluğunu artıran ana etmendir. Bu fenomen, S. typhi maruziyeti nedeni ile ortaya çıkan patolojik durumu yansıtmaktadır.Anahtar sözcükler: B220 + hücreleri, CD4 + T hücreleri, Salmonella typhi, splenektomi. Objectives: This study aims to determine the quantitative alterations of relative density of bone marrow B220 + cells and CD4 + T cells in BALB/c mice which underwent splenectomy and exposed to Salmonella typhi (S. typhi). Materials and methods: Splenectomy was performed under ketamine anesthesia (65 mg/kg BW). Exposure of S. typhi was performed by injection of acute doses (109 cells/mL) at two weeks after splenectomy and repeated at two weeks after the initial dose. The relative density of bone marrow B220 + cells and CD4 + T cells were quantified by BD FACSCalibur TM flow cytometer. Statistical analysis was performed using two-way ANOVA and Tukey HSD test. A p value of <0.05 was considered significant. Conclusion:These results indicated that splenectomy was the leading factor affecting the relative density of B220 + cells, rather than S. typhi exposure, whereas Salmonella typhi exposure was the main factor which increased the relative density of CD4 + T cells. This phenomenon also reflects the pathological condition due to S. typhi exposure.

show abstract

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Cited by 74 publications

References 82 publications

Activation of NF-κB-dependent gene expression by Salmonella flagellins FliC and FljB

Activation of NF-κB-dependent gene expression by Salmonella flagellins FliC and FljB

Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium

Splenectomy and Salmonella Typhi Exposure Lead to Quantitative Alterations of Bone Marrow B220+ Cells and CD4+ T Cells on BALB/c Mice

Contact Info

Product

Resources

About