scholarly journals Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

2020 ◽  
Author(s):  
Chuan Yu ◽  
Fuyu Du ◽  
Chunjie Zhang ◽  
Yinju Li ◽  
Chengshui Liao ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Salmonella Enterica ◽  
Caspase 3 ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Caspase 8 ◽  
Wild Type ◽  
Caspase 9 ◽  
Serovar Typhimurium ◽  
The Relationship

Abstract Background: Salmonella enterica serovar Typhimurium ( S. Typhimurium) is an important infectious disease pathogen that can survive and replicate in macrophages. Glycolysis is essential for immune responses against S. Typhimurium infection in macrophages, and is also associated with apoptosis. S. Typhimurium secreted effector K3 (SseK3) was recently identified as a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis in cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in S. Typhimurium-infected macrophages. Results: Macrophages were infected with S. Typhimurium SL1344 wild-type (WT), Δ sseK3 mutant or sseK3 -complemented strain, and the effects of sseK3 on apoptosis and glycolysis were determined. The adherence and invasion in the Δ sseK3 mutant group were similar to that in the WT and sseK3 -complemented groups, indicating that SseK3 was not essential for the adherence and invasion of S. Typhimurium in macrophages. However, the percentage of apoptosis in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. Caspase-3, caspase-8, and caspase-9 enzyme activity in the Δ sseK3 mutant group were significantly lower than in the WT group and sseK3 -complemented groups, indicating that sseK3 could improve the caspase-3, caspase-8, and caspase-9 enzyme activity. We also found that there were no significant differences in pyruvic acid levels between the three groups, but the lactic acid level in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. The ATP levels in the Δ sseK3 mutant group were remarkably higher than those in the WT and sseK3 -complemented groups. These indicated that the sseK3 enhanced the level of glycolysis in macrophages infected by S. Typhimurium. Conclusions: S. Typhimurium sseK3 is likely involved in promoting macrophage apoptosis and modulating glycolysis in macrophages. Our results could improve our understanding of the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3 .

scholarly journals Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

2020 ◽  
Author(s):  
Chuan Yu ◽  
Fuyu Du ◽  
Chunjie Zhang ◽  
Yinju Li ◽  
Chengshui Liao ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Salmonella Enterica ◽  
Caspase 3 ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Caspase 8 ◽  
Wild Type ◽  
Caspase 9 ◽  
Serovar Typhimurium ◽  
The Relationship

Abstract Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important infectious disease pathogen that can survive and replicate in macrophages. Glycolysis is essential for immune responses against S. Typhimurium infection in macrophages, and is also associated with apoptosis. S. Typhimurium secreted effector K3 (SseK3) was recently identified as a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis in cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in S. Typhimurium-infected macrophages.Results: Macrophages were infected with S. Typhimurium SL1344 wild-type (WT), ΔsseK3 mutant or sseK3-complemented strain, and the effects of sseK3 on apoptosis and glycolysis were determined. The adherence and invasion in the ΔsseK3 mutant group were similar to that in the WT and sseK3-complemented groups, indicating that SseK3 was not essential for the adherence and invasion of S. Typhimurium in macrophages. However, the percentage of apoptosis in the ΔsseK3 mutant group was much lower than that in the WT and sseK3-complemented groups. Caspase-3, caspase-8, and caspase-9 enzyme activity in the ΔsseK3 mutant group were significantly lower than in the WT group and sseK3-complemented groups, indicating that sseK3 could improve the caspase-3, caspase-8, and caspase-9 enzyme activity. We also found that there were no significant differences in pyruvic acid levels between the three groups, but the lactic acid level in the ΔsseK3 mutant group was much lower than that in the WT and sseK3-complemented groups. The ATP levels in the ΔsseK3 mutant group were remarkably higher than those in the WT and sseK3-complemented groups. These indicated that the sseK3 enhanced the level of glycolysis in macrophages infected by S. Typhimurium.Conclusions: S. Typhimurium sseK3 is likely involved in promoting macrophage apoptosis and modulating glycolysis in macrophages. Our results could improve our understanding of the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3.

scholarly journals The Salmonella enterica serovar Typhimurium sseK3 induce cell apoptosis and enhance glycolysis in macrophages

2020 ◽  
Author(s):  
Chuan Yu ◽  
Fuyu Du ◽  
Chunjie Zhang ◽  
Yinju Li ◽  
Chengshui Liao ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Acid Level ◽  
Caspase 3 ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Caspase 8 ◽  
Wild Type ◽  
Caspase 9 ◽  
Serovar Typhimurium ◽  
The Relationship

Abstract Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important infectious disease pathogen. Recently, there are increasing researches about the relationship between apoptosis and glycolysis of cells. Previous studies have identified that S. Typhimurium secreted effector K3 (SseK3) is a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis of cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in macrophages. Results: The S. Typhimurium SL1344 wild-type (WT) group, ΔsseK3 mutant group and sseK3-complemented group were used to infect macrophages and the effects of sseK3 on apoptosis and glycolysis of macrophages were investigated. The adherence and invasion of ΔsseK3 mutant group for macrophages were similar to WT group and sseK3-complemented group, indicating that SseK3 did not play an important role in the adherence and invasion of S. Typhimurium for macrophages. However, the apoptosis percentage of the ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group using flow cytometry. The caspase-3, caspase-8 and caspase-9 enzyme activity of the ΔsseK3 mutant group were decreased significantly compared with WT group and sseK3-complemented group, which suggested that sseK3 could improve the activities of caspase-3, caspase-8 and caspase-9 enzyme. We also found that the pyruvic acid level did not significantly change among ΔsseK3 mutant group, WT group and sseK3-complemented group, but the lactic acid level of ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group. The ATP level of ΔsseK3 mutant group was remarkably higher than WT group and sseK3-complemented group. These indicated that the sseK3 enhanced the level of glycolysis of macrophages infected by S. Typhimurium. Conclusions: Our data showed that the sseK3 of S. Typhimurium involved in promoting macrophages apoptosis and influencing glycolysis levels of macrophages. These results may give a better clue about the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3.

scholarly journals Salmonella enterica serovar Typhimurium sseK3 induce cell apoptosis and enhance glycolysis in macrophages

2019 ◽  
Author(s):  
Fuyu Du ◽  
Chuan Yu ◽  
Chunjie Zhang ◽  
Yinju Li ◽  
Chengshui Liao ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Acid Level ◽  
Caspase 3 ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Caspase 8 ◽  
Lactic Acid Level ◽  
Wild Type ◽  
Caspase 9 ◽  
Serovar Typhimurium ◽  
The Relationship

Abstract Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important infectious disease pathogen. Previous studies have identified that S. Typhimurium secreted effector K3 (SseK3) is a novel translated and secreted protein, but it is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in macrophages. Results: The S. Typhimurium SL1344 wild-type (WT) group, ΔsseK3 mutant group and sseK3-complemented group were used to infect macrophages and the effects of sseK3 on apoptosis and glycolysis of macrophages were investigated. The adherence and invasion of ΔsseK3 mutant group for macrophages were similar to WT group and sseK3-complemented group, indicating that SseK3 did not play an important role in the adherence and invasion of S. Typhimurium for macrophages. However, the apoptosis percentage of the ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group using flow cytometry. The caspase-3, caspase-8 and caspase-9 enzyme activity of the ΔsseK3 mutant group were decreased significantly compared with WT group and sseK3-complemented group, which suggested that sseK3 could improve the activities of caspase-3, caspase-8 and caspase-9 enzyme. We also found that the pyruvic acid level did not significantly change among ΔsseK3 mutant group, WT group and sseK3-complemented group, but the lactic acid level of ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group. The ATP level of ΔsseK3 mutant group was remarkably higher than WT group and sseK3-complemented group. These indicated that the sseK3 enhanced the level of glycolysis of macrophages infected by S. Typhimurium. Conclusions: Our data showed that the sseK3 of S. Typhimurium can promote macrophages apoptosis and influence glycolysis levels of macrophages. These results may give a better clue about the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3. Keywords: S. Typhimurium, sseK3, macrophages apoptosis, glycolysis

scholarly journals Aggregation via the Red, Dry, and Rough Morphotype Is Not a Virulence Adaptation in Salmonella enterica Serovar Typhimurium

2008 ◽  
Vol 76 (3) ◽  
pp. 1048-1058 ◽  
Author(s):  
A. P. White ◽  
D. L. Gibson ◽  
G. A. Grassl ◽  
W. W. Kay ◽  
B. B. Finlay ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Primary Role ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Cell Densities ◽  
Two Populations

ABSTRACT The Salmonella rdar (red, dry, and rough) morphotype is an aggregative and resistant physiology that has been linked to survival in nutrient-limited environments. Growth of Salmonella enterica serovar Typhimurium was analyzed in a variety of nutrient-limiting conditions to determine whether aggregation would occur at low cell densities and whether the rdar morphotype was involved in this process. The resulting cultures consisted of two populations of cells, aggregated and nonaggregated, with the aggregated cells preferentially displaying rdar morphotype gene expression. The two groups of cells could be separated based on the principle that aggregated cells were producing greater amounts of thin aggregative fimbriae (Tafi or curli). In addition, the aggregated cells retained some physiological characteristics of the rdar morphotype, such as increased resistance to sodium hypochlorite. Competitive infection experiments in mice showed that nonaggregative ΔagfA cells outcompeted rdar-positive wild-type cells in all tissues analyzed, indicating that aggregation via the rdar morphotype was not a virulence adaptation in Salmonella enterica serovar Typhimurium. Furthermore, in vivo imaging experiments showed that Tafi genes were not expressed during infection but were expressed once Salmonella was passed out of the mice into the feces. We hypothesize that the primary role of the rdar morphotype is to enhance Salmonella survival outside the host, thereby aiding in transmission.

scholarly journals Constitutive Acid Sphingomyelinase Enhances Early and Late Macrophage Killing of Salmonella enterica Serovar Typhimurium

2007 ◽  
Vol 75 (11) ◽  
pp. 5346-5352 ◽  
Author(s):  
Bruce D. McCollister ◽  
Jesse T. Myers ◽  
Jessica Jones-Carson ◽  
Dennis R. Voelker ◽  
Andrés Vázquez-Torres
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Sphingomyelinase ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Important Player ◽  
Phagocyte Oxidase ◽  
Macrophage Killing

ABSTRACT We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NADPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM. Lack of ASM activity also increased the intracellular survival of an isogenic ΔspiC::FRT Salmonella strain deficient in a translocator and effector of the Salmonella pathogenicity island 2 (SPI2) type III secretion system, suggesting that the antimicrobial activity associated with ASM is manifested regardless of the SPI2 status of the bacteria. Constitutively expressed ASM is responsible for the role that this lipid-metabolizing hydrolase plays in the innate host defense of macrophages against Salmonella. Accordingly, the ASM activity and intracellular concentration and composition of ceramide, gangliosides, and neutral sphingolipids did not increase upon Salmonella infection. Salmonella triggered, nonetheless, a significant increase in the secreted fraction of ASM. Collectively, these findings have elucidated a novel role for constitutive ASM in the anti-Salmonella activity of murine macrophages.

scholarly journals A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium

2007 ◽  
Vol 176 (3) ◽  
pp. 263-268 ◽  
Author(s):  
Adam C. Smith ◽  
Won Do Heo ◽  
Virginie Braun ◽  
Xiuju Jiang ◽  
Chloe Macrae ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Dominant Negative ◽  
Rab Gtpases ◽  
Wild Type ◽  
Intracellular Growth ◽  
Non Invasive ◽  
Serovar Typhimurium ◽  
Guanosine Triphosphatase ◽  
Kinetics Of

Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome–lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth.

scholarly journals Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance during Salmonella enterica Serovar Typhimurium Infection

2003 ◽  
Vol 71 (9) ◽  
pp. 4873-4882 ◽  
Author(s):  
Qian Li ◽  
Bobby J. Cherayil
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Peritoneal Macrophages ◽  
Phagocytic Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Serovar Typhimurium ◽  
Tlr4 Gene ◽  
Factor Alpha

ABSTRACT Toll-like receptors (TLRs) play an important role in the innate immune response, particularly in the initial interaction between the infecting microorganism and phagocytic cells, such as macrophages. We investigated the role of TLR4 during infection of primary murine peritoneal macrophages with Salmonella enterica serovar Typhimurium. We found that macrophages from the C3H/HeJ mouse strain, which carries a functionally inactive Tlr4 gene, exhibit marked impairment of tumor necrosis factor alpha (TNF-α) secretion in response to S. enterica serovar Typhimurium infection. However, activation of extracellular growth factor-regulated kinase and NF-κB signaling pathways was relatively unaffected, as was increased expression of TNF-α mRNA. Furthermore, macrophage tolerance, which is associated with increased expression of the NF-κB p50 and p52 subunits, was induced by S. enterica serovar Typhimurium even in the absence of functional TLR4. These results indicate that during infection of macrophages by S. enterica serovar Typhimurium, TLR4 signals are required at a posttranscriptional step to maximize secretion of TNF-α. Signals delivered by pattern recognition receptors other than TLR4 are sufficient for the increased expression of the TNF-α transcript and at least some genes associated with macrophage tolerance.

scholarly journals Salmonella enterica Serovar Typhimurium Uses PbgA/YejM To Regulate Lipopolysaccharide Assembly during Bacteremia

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Melina B. Cian ◽  
Nicole P. Giordano ◽  
Revathi Masilamani ◽  
Keaton E. Minor ◽  
Zachary D. Dalebroux
Keyword(s):  
Salmonella Enterica ◽  
Lipid A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Transmembrane Domain ◽  
Wild Type ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Periplasmic Domain ◽  
Inner Membrane Protein ◽  
Substitution Mutations

ABSTRACT Salmonella enterica serovar Typhimurium (S. Typhimurium) relies upon the inner membrane protein PbgA to enhance outer membrane (OM) integrity and promote virulence in mice. The PbgA transmembrane domain (residues 1 to 190) is essential for viability, while the periplasmic domain (residues 191 to 586) is dispensable. Residues within the basic region (residues 191 to 245) bind acidic phosphates on polar phospholipids, like for cardiolipins, and are necessary for salmonella OM integrity. S. Typhimurium bacteria increase their OM cardiolipin concentrations during activation of the PhoPQ regulators. The mechanism involves PbgA’s periplasmic globular region (residues 245 to 586), but the biological role of increasing cardiolipins on the surface is not understood. Nonsynonymous polymorphisms in three essential lipopolysaccharide (LPS) synthesis regulators, lapB (also known as yciM), ftsH, and lpxC, variably suppressed the defects in OM integrity, rifampin resistance, survival in macrophages, and systemic colonization of mice in the pbgAΔ191–586 mutant (in which the PbgA periplasmic domain from residues 191 to 586 is deleted). Compared to the OMs of the wild-type salmonellae, the OMs of the pbgA mutants had increased levels of lipid A-core molecules, cardiolipins, and phosphatidylethanolamines and decreased levels of specific phospholipids with cyclopropanated fatty acids. Complementation and substitution mutations in LapB and LpxC generally restored the phospholipid and LPS assembly defects for the pbgA mutants. During bacteremia, mice infected with the pbgA mutants survived and cleared the bacteria, while animals infected with wild-type salmonellae succumbed within 1 week. Remarkably, wild-type mice survived asymptomatically with pbgA-lpxC salmonellae in their livers and spleens for months, but Toll-like receptor 4-deficient animals succumbed to these infections within roughly 1 week. In summary, S. Typhimurium uses PbgA to influence LPS assembly during stress in order to survive, adapt, and proliferate within the host environment.

scholarly journals A Plasmid-Encoded FetMP-Fls Iron Uptake System Confers Selective Advantages to Salmonella enterica Serovar Typhimurium in Growth under Iron-Restricted Conditions and for Infection of Mammalian Host Cells

2020 ◽  
Vol 8 (5) ◽  
pp. 630
Author(s):  
Vanesa García ◽  
Ana Herrero-Fresno ◽  
Rosaura Rodicio ◽  
Alfonso Felipe-López ◽  
Ignacio Montero ◽  
...  
Keyword(s):  
Iron Content ◽  
Salmonella Enterica ◽  
Iron Uptake ◽  
Type Strain ◽  
Wild Type Strain ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Iron Acquisition ◽  
Clinical Strain ◽  
Wild Type ◽  
Serovar Typhimurium

The resistance plasmid pUO-StVR2, derived from virulence plasmid pSLT, is widespread in clinical isolates of Salmonella enterica serovar Typhimurium recovered in Spain and other European countries. pUO-StVR2 carries several genes encoding a FetMP-Fls system, which could be involved in iron uptake. We therefore analyzed S. Typhimurium LSP 146/02, a clinical strain selected as representative of the isolates carrying the plasmid, and an otherwise isogenic mutant lacking four genes (fetMP-flsDA) of the fetMP-fls region. Growth curves and determination of the intracellular iron content under iron-restricted conditions demonstrated that deletion of these genes impairs iron acquisition. Thus, under these conditions, the mutant grew significantly worse than the wild-type strain, its iron content was significantly lower, and it was outcompeted by the wild-type strain in competition assays. Importantly, the strain lacking the fetMP-flsDA genes was less invasive in cultured epithelial HeLa cells and replicated poorly upon infection of RAW264.7 macrophages. The genes were introduced into S. Typhimurium ATCC 14028, which lacks the FetMP-Fls system, and this resulted in increased growth under iron limitation as well as an increased ability to multiply inside macrophages. These findings indicate that the FetMP-Fls iron acquisition system exceeds the benefits conferred by the other high-affinity iron uptake systems carried by ATCC 14028 and LSP 146/02. We proposed that effective iron acquisition by this system in conjunction with antimicrobial resistance encoded from the same plasmid have greatly contributed to the epidemic success of S. Typhimurium isolates harboring pUO-StVR2.

scholarly journals Flagella and Chemotaxis Are Required for Efficient Induction of Salmonella enterica Serovar Typhimurium Colitis in Streptomycin-Pretreated Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4138-4150 ◽  
Author(s):  
Bärbel Stecher ◽  
Siegfried Hapfelmeier ◽  
Catherine Müller ◽  
Marcus Kremer ◽  
Thomas Stallmach ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Innate Immune ◽  
Gastrointestinal Infections ◽  
Infection Models ◽  
Serovar Typhimurium ◽  
Efficient Induction ◽  
Toll Like Receptor 5

ABSTRACT Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.

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