scholarly journals β-Galactomannan and Saccharomyces cerevisiae var. boulardii Modulate the Immune Response against Salmonella enterica Serovar Typhimurium in Porcine Intestinal Epithelial and Dendritic Cells

2012 ◽  
Vol 19 (3) ◽  
pp. 368-376 ◽  
Author(s):  
Roger Badia ◽  
M. Teresa Brufau ◽  
Ana Maria Guerrero-Zamora ◽  
Rosil Lizardo ◽  
Irina Dobrescu ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dendritic Cells ◽  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Gm Csf ◽  
Tnf Α ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericaserovar Typhimurium is a facultative intracellular pathogen that causes inflammation, necrosis, and diarrhea in pigs, as well as being an important source of food-borne diseases in humans. Probiotics and prebiotics are promising alternatives to antibiotics to control and prevent intestinal infections. The present work investigated a recently developed β-galactomannan (βGM) prebiotic compared to the proven probioticSaccharomyces cerevisiaevar.boulardiion porcine ileum intestinal epithelial cells (IECs) of the IPI-2I line and monocyte-derived dendritic cells (DCs) coculturedin vitrowithSalmonella. We observed that bothS. cerevisiaevar.boulardiiand βGM inhibited the association ofSalmonellawith IECsin vitro. Our data indicated that βGM has a higher ability thanS. cerevisiaevar.boulardiito inhibitSalmonella-induced proinflammatory mRNA (cytokines tumor necrosis factor alpha [TNF-α], interleukin-1α [IL-1α], IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF] and chemokines CCL2, CCL20, and CXCL8) and at protein levels (IL-6 and CXCL8). Additionally, βGM andS. cerevisiaevar.boulardiiinduced some effects on DCs that were not observed on IECs: βGM andS. cerevisiaevar.boulardiishowed slight upregulation of mRNA for TNF-α, GM-CSF, and CCR7 receptor on porcine monocyte-derived dendritic cells (DCs). Indeed, the addition of βGM orS. cerevisiaevar.boulardiion DCs cocultured withSalmonellashowed higher gene expression (mRNA) for TNF-α, GM-CSF, and CXCL8 compared to that of the control withSalmonella. In conclusion, the addition of βGM inhibitsSalmonella-induced proinflammatory profiles in IECs but may promote DC activation, although associated molecular mechanisms remain to be elucidated.

scholarly journals Salmonella enterica Infection of Murine and Human Enteroid-Derived Monolayers Elicits Differential Activation of Epithelium-Intrinsic Inflammasomes

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Mayumi K. Holly ◽  
Xiao Han ◽  
Edward J. Zhao ◽  
Shauna M. Crowley ◽  
Joannie M. Allaire ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Bacterial Infections ◽  
Intestinal Epithelial ◽  
Major Pathway ◽  
Content Type ◽  
Caspase 1 ◽  
Serovar Typhimurium ◽  
Multiple Species ◽  
Inflammatory Caspases

ABSTRACT Recent studies have determined that inflammasome signaling plays an important role in driving intestinal epithelial cell (IEC) responses to bacterial infections, such as Salmonella enterica serovar Typhimurium. There are two primary inflammasome pathways, canonical (involving caspase-1) and noncanonical (involving caspase-4 and -5 in humans and caspase-11 in mice). Prior studies identified the canonical inflammasome as the major pathway leading to interleukin-18 (IL-18) release and restriction of S. Typhimurium replication in the mouse cecum. In contrast, the human C2Bbe1 colorectal carcinoma cell line expresses little caspase-1 but instead utilizes caspase-4 to respond to S. Typhimurium infection. Intestinal enteroid culture has enabled long-term propagation of untransformed IECs from multiple species, including mouse and human. Capitalizing on this technology, we used a genetic approach to directly compare the relative importance of different inflammatory caspases in untransformed mouse and human IECs and transformed human IECs upon S. Typhimurium infection in vitro. We show that caspase-1 is important for restricting intracellular S. Typhimurium replication and initiating IL-18 secretion in mouse IECs but is dispensable in human IECs. In contrast, restriction of intracellular S. Typhimurium and production of IL-18 are dependent on caspase-4 in both transformed and untransformed human IECs. Notably, cytosolic replication in untransformed cells from both species was less pronounced than in transformed human cells, suggesting that transformation may impact additional pathways that restrict S. Typhimurium replication. Taken together, these data highlight the differences between mouse and human IECs and the utility of studying transformed and untransformed cells in parallel.

scholarly journals Global Transcriptome and Mutagenic Analyses of the Acid Tolerance Response of Salmonella enterica Serovar Typhimurium

2015 ◽  
Vol 81 (23) ◽  
pp. 8054-8065 ◽  
Author(s):  
Daniel Ryan ◽  
Niladri Bhusan Pati ◽  
Urmesh K. Ojha ◽  
Chandrashekhar Padhi ◽  
Shilpa Ray ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Acid Stress ◽  
Acid Tolerance ◽  
Differentially Expressed ◽  
Acid Tolerance Response ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Tolerance Response

ABSTRACTSalmonella entericaserovar Typhimurium (S. Typhimurium) is one of the leading causative agents of food-borne bacterial gastroenteritis. Swift invasion through the intestinal tract and successful establishment in systemic organs are associated with the adaptability ofS. Typhimurium to different stress environments. Low-pH stress serves as one of the first lines of defense in mammalian hosts, whichS. Typhimurium must efficiently overcome to establish an infection. Therefore, a better understanding of the molecular mechanisms underlying the adaptability ofS. Typhimurium to acid stress is highly relevant. In this study, we have performed a transcriptome analysis ofS. Typhimurium under the acid tolerance response (ATR) and found a large number of genes (∼47%) to be differentially expressed (more than 1.5-fold or less than −1.5-fold;P< 0.01). Functional annotation revealed differentially expressed genes to be associated with regulation, metabolism, transport and binding, pathogenesis, and motility. Additionally, our knockout analysis of a subset of differentially regulated genes facilitated the identification of proteins that contribute toS. Typhimurium ATR and virulence. Mutants lacking genes encoding the K+binding and transport protein KdpA, hypothetical protein YciG, the flagellar hook cap protein FlgD, and the nitrate reductase subunit NarZ were significantly deficient in their ATRs and displayed variedin vitrovirulence characteristics. This study offers greater insight into the transcriptome changes ofS. Typhimurium under the ATR and provides a framework for further research on the subject.

scholarly journals Salmonellainfection inhibits intestinal biotin transport: cellular and molecular mechanisms

2015 ◽  
Vol 309 (2) ◽  
pp. G123-G131 ◽  
Author(s):  
Abhisek Ghosal ◽  
Stefan Jellbauer ◽  
Rubina Kapadia ◽  
Manuela Raffatellu ◽  
Hamid M. Said
Keyword(s):  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Significant Inhibition ◽  
Intestinal Epithelial ◽  
Food Borne ◽  
Tnf Α ◽  
Sodium Dependent ◽  
Serovar Typhimurium

Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium ( S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines.

scholarly journals Terminal Deoxynucleotidyl Transferase Is Not Required for Antibody Response to Polysaccharide Vaccines againstStreptococcus pneumoniaeandSalmonella entericaSerovar Typhi

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Vivek Belde ◽  
Matthew P. Cravens ◽  
Dania Gulandijany ◽  
Justin A. Walker ◽  
Isabel Palomo-Caturla ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Salmonella Enterica ◽  
Passive Immunization ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human Infants ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTB cell antigen receptor (BCR) diversity increases by several orders of magnitude due to the action of terminal deoxynucleotidyl transferase (TdT) during V(D)J recombination. Unlike adults, infants have limited BCR diversity, in part due to reduced expression of TdT. Since human infants and young mice respond poorly to polysaccharide vaccines, such as the pneumococcal polysaccharide vaccine Pneumovax23 and Vi polysaccharide (ViPS) ofSalmonella entericaserovar Typhi, we tested the contribution of TdT-mediated BCR diversity in response to these vaccines. We found that TdT+/−and TdT−/−mice generated comparable antibody responses to Pneumovax23 and survivedStreptococcus pneumoniaechallenge. Moreover, passive immunization of B cell-deficient mice with serum from Pneumovax23-immunized TdT+/−or TdT−/−mice conferred protection. TdT+/−and TdT−/−mice generated comparable levels of anti-ViPS antibodies and antibody-dependent, complement-mediated bactericidal activity againstS. Typhiin vitro. To test the protective immunity conferred by ViPS immunizationin vivo, TdT+/−and TdT−/−mice were challenged with a chimericSalmonella entericaserovar Typhimurium strain expressing ViPS, since mice are nonpermissive hosts forS. Typhi infection. Compared to their unimmunized counterparts, immunized TdT+/−and TdT−/−mice challenged with ViPS-expressingS. Typhimurium exhibited a significant reduction in the bacterial burden and liver pathology. These data suggest that the impaired antibody response to the Pneumovax23 and ViPS vaccines in the young is not due to limited TdT-mediated BCR diversification.

scholarly journals Salmonella enterica Serovar Typhimurium Alters the Extracellular Proteome of Macrophages and Leads to the Production of Proinflammatory Exosomes

2017 ◽  
Vol 86 (2) ◽  
Author(s):  
Winnie W. Hui ◽  
Kamil Hercik ◽  
Sayali Belsare ◽  
Navatha Alugubelly ◽  
Beata Clapp ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Phagocytic Cells ◽  
Macrophage Infection ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Gm Csf ◽  
Extracellular Milieu ◽  
Extracellular Proteome ◽  
Serovar Typhimurium ◽  
Canonical Pathways

ABSTRACTSalmonella entericaserovar Typhimurium is a Gram-negative bacterium, which can invade and survive within macrophages. Pathogenic salmonellae induce the secretion of specific cytokines from these phagocytic cells and interfere with the host secretory pathways. In this study, we describe the extracellular proteome of human macrophages infected withS. Typhimurium, followed by analysis of canonical pathways of proteins isolated from the extracellular milieu. We demonstrate that some of the proteins secreted by macrophages uponS. Typhimurium infection are released via exosomes. Moreover, we show that infected macrophages produce CD63+and CD9+subpopulations of exosomes at 2 h postinfection. Exosomes derived from infected macrophages trigger the Toll-like receptor 4-dependent release of tumor necrosis factor alpha (TNF-α) from naive macrophages and dendritic cells, but they also stimulate secretion of such cytokines as RANTES, IL-1ra, MIP-2, CXCL1, MCP-1, sICAM-1, GM-CSF, and G-CSF. Proinflammatory effects of exosomes are partially attributed to lipopolysaccharide, which is encapsulated within exosomes. In summary, we show for the first time that proinflammatory exosomes are formed in the early phase of macrophage infection withS. Typhimurium and that they can be used to transfer cargo to naive cells, thereby leading to their stimulation.

scholarly journals Butyrate Specifically Down-Regulates Salmonella Pathogenicity Island 1 Gene Expression

2006 ◽  
Vol 72 (1) ◽  
pp. 946-949 ◽  
Author(s):  
I. Gantois ◽  
R. Ducatelle ◽  
F. Pasmans ◽  
F. Haesebrouck ◽  
I. Hautefort ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial Cells ◽  
Pathogenicity Island ◽  
Effector Protein ◽  
Intestinal Epithelial ◽  
Penicillin Binding Protein ◽  
Serovar Typhimurium ◽  
Separate Site ◽  
Comparative Transcriptomic Analysis

ABSTRACT Invasion of intestinal epithelial cells by Salmonella enterica is decreased after exposure to butyric acid. To understand the molecular mechanisms of this phenomenon, a comparative transcriptomic analysis of Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium grown in medium supplemented with butyrate was performed. We found that butyrate down-regulated the expression of 19 genes common to both serovars by a factor of twofold or more, and 17 of these genes localized to the Salmonella pathogenicity island 1 (SPI1). These included the SPI1 regulatory genes hilD and invF. Of the remaining two genes, ampH has 91% homology to an Escherichia coli penicillin-binding protein and sopE2 encodes a type III-secreted effector protein associated with invasion but located at a separate site on the chromosome from SPI1.

scholarly journals Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

2011 ◽  
Vol 79 (7) ◽  
pp. 2554-2566 ◽  
Author(s):  
Winnie W. S. Kum ◽  
Bernard C. Lo ◽  
Hong B. Yu ◽  
B. Brett Finlay
Keyword(s):  
Salmonella Enterica ◽  
Annexin V ◽  
Immunohistochemical Analysis ◽  
Neutrophil Infiltration ◽  
Protective Role ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTTheSalmonellaeffector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosisin vitro. To characterize the role of Akt2 in host defense againstSalmonella entericaserovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using aSalmonellaacute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1+CD11b+neutrophils and F4/80+CD11b+macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V+and terminal transferase dUTP nick end labeling-positive (TUNEL+) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WTSalmonellawere abolished when these mice were infected with thesopBdeletion mutant, indicating that SopB may play a role in protecting the mice fromSalmonellainfection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 inSalmonellainfection.

scholarly journals Lipopolysaccharides Belonging to Different Salmonella Serovars Are Differentially Capable of Activating Toll-Like Receptor 4

2014 ◽  
Vol 82 (11) ◽  
pp. 4553-4562 ◽  
Author(s):  
Daniela Chessa ◽  
Luisella Spiga ◽  
Nicola De Riu ◽  
Paola Delaconi ◽  
Vittorio Mazzarello ◽  
...  
Keyword(s):  
Immune Response ◽  
Salmonella Enterica ◽  
Systemic Infection ◽  
Embryonic Cell ◽  
Limited Information ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericasubsp.entericaserovar (serotype) Abortusovis is a member of theEnterobacteriaceae. This serotype is naturally restricted to ovine species and does not infect humans. Limited information is available about the immune response of sheep toS. Abortusovis.S. Abortusovis, likeSalmonella entericasubsp.entericaserovar Typhi, causes a systemic infection in which, under natural conditions, animals are not able to raise a rapid immune response. Failure to induce the appropriate response allows pathogens to reach the placenta and results in an abortion. Lipopolysaccharides (LPSs) are pathogen-associated molecular patterns (PAMPs) that are specific to bacteria and are not synthesized by the host. Toll-like receptors (TLRs) are a family of receptors that specifically recognize PAMPs. As a first step, we were able to identify the presence of Toll-like receptor 4 (TLR4) on the ovine placenta by using an immunohistochemistry technique. To our knowledge, this is the first work describing the interaction betweenS. Abortusovis LPS and TLR4. Experiments using an embryonic cell line (HEK293) transfected with human and ovine TLR4s showed a reduction of interleukin 8 (IL-8) production byS. Abortusovis andSalmonella entericasubsp.entericaserovar Paratyphi upon LPS stimulation compared toSalmonella entericasubsp.entericaserovar Typhimurium. Identical results were observed using heat-killed bacteria instead of LPS. Based on data obtained with TLR4in vitrostimulation, we demonstrated that the serotypeS. Abortusovis is able to successfully evade the immune system whereasS. Typhimurium and other serovars fail to do so.

scholarly journals Role of Nod1 in Mucosal Dendritic Cells during Salmonella Pathogenicity Island 1-Independent Salmonella enterica Serovar Typhimurium Infection

2009 ◽  
Vol 77 (10) ◽  
pp. 4480-4486 ◽  
Author(s):  
Lionel Le Bourhis ◽  
Joao Gamelas Magalhaes ◽  
Thirumahal Selvanantham ◽  
Leonardo H. Travassos ◽  
Kaoru Geddes ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lamina Propria ◽  
Salmonella Enterica ◽  
Severe Disease ◽  
Bacterial Pathogen ◽  
Critical Function ◽  
Intestinal Lamina Propria ◽  
Serovar Typhimurium

ABSTRACT Recent advances in immunology have highlighted the critical function of pattern-recognition molecules (PRMs) in generating the innate immune response to effectively target pathogens. Nod1 and Nod2 are intracellular PRMs that detect peptidoglycan motifs from the cell walls of bacteria once they gain access to the cytosol. Salmonella enterica serovar Typhimurium is an enteric intracellular pathogen that causes a severe disease in the mouse model. This pathogen resides within vacuoles inside the cell, but the question of whether cytosolic PRMs such as Nod1 and Nod2 could have an impact on the course of S. Typhimurium infection in vivo has not been addressed. Here, we show that deficiency in the PRM Nod1, but not Nod2, resulted in increased susceptibility toward a mutant strain of S. Typhimurium that targets directly lamina propria dendritic cells (DCs) for its entry into the host. Using this bacterium and bone marrow chimeras, we uncovered a surprising role for Nod1 in myeloid cells controlling bacterial infection at the level of the intestinal lamina propria. Indeed, DCs deficient for Nod1 exhibited impaired clearance of the bacteria, both in vitro and in vivo, leading to increased organ colonization and decreased host survival after oral infection. Taken together, these findings demonstrate a key role for Nod1 in the host response to an enteric bacterial pathogen through the modulation of intestinal lamina propria DCs.

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