scholarly journals Salmonella Exploits Caspase-1 to Colonize Peyer's Patches in a Murine Typhoid Model

2000 ◽  
Vol 192 (2) ◽  
pp. 249-258 ◽  
Author(s):  
Denise M. Monack ◽  
David Hersh ◽  
Nafisa Ghori ◽  
Donna Bouley ◽  
Arturo Zychlinsky ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mammalian Cells ◽  
Yersinia Pseudotuberculosis ◽  
Lethal Dose ◽  
Cysteine Proteases ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
M Cell ◽  
Caspase 1

Salmonella typhimurium invades host macrophages and induces apoptosis and the release of mature proinflammatory cytokines. SipB, a protein translocated by Salmonella into the cytoplasm of macrophages, is required for activation of Caspase-1 (Casp-1, an interleukin [IL]-1β–converting enzyme), which is a member of a family of cysteine proteases that induce apoptosis in mammalian cells. Casp-1 is unique among caspases because it also directly cleaves the proinflammatory cytokines IL-1β and IL-18 to produce bioactive cytokines. We show here that mice lacking Casp-1 (casp-1−/− mice) had an oral S. typhimurium 50% lethal dose (LD50) that was 1,000-fold higher than that of wild-type mice. Salmonella breached the M cell barrier of casp-1−/− mice efficiently; however, there was a decrease in the number of apoptotic cells, intracellular bacteria, and the recruitment of polymorphonuclear lymphocytes in the Peyer's patches (PP) as compared with wild-type mice. Furthermore, Salmonella did not disseminate systemically in the majority of casp-1−/− mice, as demonstrated by significantly less colonization in the PP, mesenteric lymph nodes, and spleens of casp-1−/− mice after an oral dose of S. typhimurium that was 100-fold higher than the LD50. The increased resistance in casp-1−/− animals appears specific for Salmonella infection since these mice were susceptible to colonization by another enteric pathogen, Yersinia pseudotuberculosis, which normally invades the PP. These results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice.

scholarly journals The Proinflammatory Response Induced by Wild-Type Yersinia pseudotuberculosis Infection Inhibits Survival of yop Mutants in the Gastrointestinal Tract and Peyer's Patches

2006 ◽  
Vol 74 (3) ◽  
pp. 1516-1527 ◽  
Author(s):  
Lauren K. Logsdon ◽  
Joan Mecsas
Keyword(s):  
Yersinia Pseudotuberculosis ◽  
Intestinal Inflammation ◽  
Peyer's Patches ◽  
Host Responses ◽  
Infection Model ◽  
Peyer’S Patches ◽  
Wild Type ◽  
Single Strain ◽  
Infection Models ◽  
Ifn Γ

ABSTRACT Single-strain infections and coinfections are frequently used to assess roles of virulence factors in infected tissues. After oral inoculation of mice, Yersinia pseudotuberculosis yopE and yopH mutants colonize the intestines and Peyer's patches in single-strain infections but fail to persist in competition with wild-type Y. pseudotuberculosis, indicating that these two infection models provide different insights into the roles of Yops. To determine how wild-type Y. pseudotuberculosis hinders yop mutant survival, yop mutant colonization and host responses were investigated in several different infection models that isolated specific features of wild-type Y. pseudotuberculosis infection. Infection with wild-type Y. pseudotuberculosis caused significantly more inflammation than yop mutants. Results from coinfections of gamma interferon (IFN-γ)−/− mice revealed that IFN-γ-regulated defenses target these mutants, suggesting that YopE and YopH protect Y. pseudotuberculosis from these defenses in BALB/c mice. We developed an oral-intraperitoneal infection model to evaluate the effects of spleen and liver colonization by Y. pseudotuberculosis on yop mutants in the intestines. Spleen and liver infection increased inflammation and decreased yop mutant survival in the intestines, indicating that infection of these organs has consequences in intestinal tissues. Finally, competition infections with Y. pseudotuberculosis mutants with various abilities to induce inflammation demonstrated that survival of the yopE, but not the yopH, mutant was consistently decreased in inflamed tissues. In summary, infection with Y. pseudotuberculosis in intestinal and systemic sites induces intestinal inflammation, which decreases yop mutant survival. Thus, competition studies with wild-type yersiniae reveal critical roles of Yops in combating host responses to a normal virulent infection.

scholarly journals The rovA Mutant of Yersinia enterocolitica Displays Differential Degrees of Virulence Depending on the Route of Infection

2003 ◽  
Vol 71 (6) ◽  
pp. 3512-3520 ◽  
Author(s):  
Peter H. Dube ◽  
Scott A. Handley ◽  
Paula A. Revell ◽  
Virginia L. Miller
Keyword(s):  
Yersinia Enterocolitica ◽  
Inflammatory Disease ◽  
Inflammatory Responses ◽  
Systemic Disease ◽  
Lethal Dose ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
Global Regulator ◽  
Kinetics Of

ABSTRACT Yersinia enterocolitica is an invasive enteric pathogen that causes significant inflammatory disease. Recently, we identified and characterized a global regulator of virulence (rovA). When mice are infected orally with the rovA mutant they are attenuated by 50% lethal dose (LD50) analysis and have altered kinetics of infection. Most significantly, mice orally infected with the rovA mutant have greatly reduced inflammation in the Peyer's patches compared to those infected with wild-type Y. enterocolitica. However, we present data here indicating that when the rovA mutant bacteria are delivered intraperitoneally (i.p.), they are significantly more virulent than when delivered orally. The i.p. LD50 for the rovA mutant is only 10-fold higher than that of the wild-type Y. enterocolitica, and there are significant inflammatory responses to the rovA mutant that are evident in the liver and spleen. Altogether, these data suggest that the RovA regulon may be required for the early events of the infection that occur in the Peyer's patches. Furthermore, these data suggest that the RovA regulon may be dispensable for Y. enterocolitica systemic disease and inflammatory responses if the Peyer's patches are bypassed.

scholarly journals Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosis in Mice

2000 ◽  
Vol 68 (5) ◽  
pp. 2553-2559 ◽  
Author(s):  
Christophe Carnoy ◽  
Chantal Mullet ◽  
Heide Müller-Alouf ◽  
Emmanuelle Leteurtre ◽  
Michel Simonet
Keyword(s):  
Yersinia Pseudotuberculosis ◽  
Systemic Infection ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
Bacterial Inoculation ◽  
Mesenteric Lymph Nodes ◽  
Strain Determination ◽  
Mouse Model Of Infection

ABSTRACT Yersinia pseudotuberculosis, a gram-negative bacterium responsible for enteric and systemic infection in humans, produces a superantigenic toxin designated YPMa (Y. pseudotuberculosis-derived mitogen). To assess the role of YPMa in the pathogenesis of Y. pseudotuberculosis, we constructed a superantigen-deficient mutant and compared its virulence in a mouse model of infection to the virulence of the wild-type strain. Determination of the survival rate after intravenous (i.v.) bacterial inoculation of OF1 mice clearly showed that inactivation ofypmA, encoding YPMa, reduced the virulence of Y. pseudotuberculosis. Mice infected i.v. with 104 and 105 wild-type bacteria died within 9 days, whereas mice infected with the ypmA mutant survived 12 and 3 days longer, respectively. This decreased virulence of the ypmAmutant strain was not due to an impaired colonization of the spleen, liver, or lungs. In contrast to i.v. challenge, bacterial inoculation by the intragastric (i.g.) route did not reveal any difference in virulence between wild-type Y. pseudotuberculosis and theypmA mutant since the 50% lethal doses were identical for both strains. Moreover, inactivation of ypmA gene did not affect the bacterial growth of Y. pseudotuberculosis in Peyer's patches, mesenteric lymph nodes (MLNs), and spleen after oral infection. Histological studies of spleen, liver, lungs, heart, Peyer's patches, and MLNs after i.v. or i.g. challenge with the wild type or the ypmA mutant did not reveal any feature that can be specifically related to YPMa. Our data show that the superantigenic toxin YPMa contributes to the virulence of Y. pseudotuberculosis in systemic infection in mice.

scholarly journals Role of Immunoglobulin A in Protection against Reovirus Entry into Murine Peyer's Patches

2001 ◽  
Vol 75 (22) ◽  
pp. 10870-10879 ◽  
Author(s):  
Katherine J. Silvey ◽  
Amy B. Hutchings ◽  
Michael Vajdy ◽  
Mary M. Petzke ◽  
Marian R. Neutra
Keyword(s):  
Viral Entry ◽  
Immunoglobulin A ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
M Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Adult Mice ◽  
Reovirus Type

ABSTRACT Reovirus type 1 Lang (T1L) infects the mouse intestinal mucosa by adhering specifically to epithelial M cells and exploiting M-cell transport to enter the Peyer's patches. Oral inoculation of adult mice has been shown to elicit cellular and humoral immune responses that clear the infection within 10 days. This study was designed to determine whether adult mice that have cleared a primary infection are protected against viral entry upon oral rechallenge and, if so, whether antireovirus secretory immunoglobulin A (S-IgA) is a necessary component of protection. Adult BALB/c mice that were orally inoculated on day 0 with reovirus T1L produced antiviral S-IgA in feces and IgG in serum directed primarily against the reovirus ς1 attachment protein. Eight hours after oral reovirus challenge on day 21, the Peyer's patches of previously exposed mice contained no detectable virus whereas Peyer's patches of naive controls contained up to 2,300 PFU of reovirus/mg of tissue. Orally inoculated IgA knockout (IgA−/−) mice cleared the initial infection as effectively as wild-type mice and produced higher levels of reovirus-specific serum IgG and secretory IgM than C57BL/6 wild-type mice. When IgA−/− mice were rechallenged on day 21, however, their Peyer's patches became infected. These results indicate that intestinal S-IgA is an essential component of immune protection against reovirus entry into Peyer's patch mucosa.

scholarly journals Structural Features of and Cholesterol Distribution in M-Cell Membranes in Guinea Pig, Rat, and Mouse Peyer's Patches

1984 ◽  
Vol 87 (5) ◽  
pp. 1091-1103 ◽  
Author(s):  
James L. Madara ◽  
William A. Bye ◽  
Jerry S. Trier
Keyword(s):  
Guinea Pig ◽  
Cell Membranes ◽  
Structural Features ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
M Cell

Oral immunization with a dam mutant of Yersinia pseudotuberculosis protects against plague

Microbiology ◽  
2005 ◽  
Vol 151 (6) ◽  
pp. 1919-1926 ◽  
Author(s):  
Victoria L. Taylor ◽  
Richard W. Titball ◽  
Petra C. F. Oyston
Keyword(s):  
Gene Expression ◽  
Bile Salts ◽  
Yersinia Pseudotuberculosis ◽  
Lethal Dose ◽  
Oral Immunization ◽  
Wild Type ◽  
Gene Encoding ◽  
Serovar Typhimurium ◽  
Dna Adenine Methylase ◽  
Methylase Gene

Inactivation of the gene encoding DNA adenine methylase (dam) has been shown to attenuate some pathogens such as Salmonella enterica serovar Typhimurium and is a lethal mutation in others such as Yersinia pseudotuberculosis strain YPIII. In this study the dam methylase gene in Yersinia pseudotuberculosis strain IP32953 was inactivated. Unlike the wild-type, DNA isolated from the mutant could be digested with MboI, which is consistent with an altered pattern of DNA methylation. The mutant was sensitive to bile salts but not to 2-aminopurine. The effect of dam inactivation on gene expression was examined using a DNA microarray. In BALB/c mice inoculated orally or intravenously with the dam mutant, the median lethal dose (MLD) was at least 106-fold higher than the MLD of the wild-type. BALB/c mice inoculated with the mutant were protected against a subcutaneous challenge with 100 MLDs of Yersinia pestis strain GB and an intravenous challenge with 300 MLDs of Y. pseudotuberculosis IP32953.

scholarly journals Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

2016 ◽  
Vol 84 (4) ◽  
pp. 1062-1072 ◽  
Author(s):  
Taylor J. Schoberle ◽  
Lawton K. Chung ◽  
Joseph B. McPhee ◽  
Ben Bogin ◽  
James B. Bliska
Keyword(s):  
Yersinia Pseudotuberculosis ◽  
Host Cells ◽  
Enzyme Release ◽  
Activated Macrophages ◽  
Innate Immune Responses ◽  
Wild Type ◽  
Content Type ◽  
Caspase 1 ◽  
Epistasis Analysis ◽  
Dependent Mechanism

PathogenicYersiniaspecies utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promoteYersiniapathogenesis. In turn,Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior toYersinia pseudotuberculosisinfection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of aY. pseudotuberculosisyopMmutant was compared to that of ayopJ yopM,yopE yopM,yopH yopM,yopT yopM, orypkA yopMmutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutantY. pseudotuberculosisstrains. Results show enhanced activation of caspase-1 after infection with theyopJ yopMmutant relative to infection by any other single or double mutant. Similar results were obtained with theyopJ,yopM, andyopJ yopMmutants ofYersinia pestis. Following intravenous infection of mice, theY. pseudotuberculosisyopJmutant was as virulent as the wild type, while theyopJ yopMmutant was significantly more attenuated than theyopMmutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promotingYersiniavirulence.

scholarly journals In Vivo-Induced InvA-Like Autotransporters Ifp and InvC of Yersinia pseudotuberculosis Promote Interactions with Intestinal Epithelial Cells and Contribute to Virulence

2011 ◽  
Vol 80 (3) ◽  
pp. 1050-1064 ◽  
Author(s):  
Fabio Pisano ◽  
Annika Kochut ◽  
Frank Uliczka ◽  
Rebecca Geyer ◽  
Tatjana Stolz ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Yersinia Pseudotuberculosis ◽  
Intestinal Epithelial Cells ◽  
Bacterial Colonization ◽  
Immune Defense ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Intestinal Epithelial ◽  
Content Type ◽  
K 12

TheYersinia pseudotuberculosisIfp and InvC molecules are putative autotransporter proteins with a high homology to the invasin (InvA) protein. To characterize the function of these surface proteins, we expressed both factors inEscherichia coliK-12 and demonstrated the attachment of Ifp- and InvC-expressing bacteria to human-, mouse-, and pig-derived intestinal epithelial cells. Ifp also was found to mediate microcolony formation and internalization into polarized human enterocytes. TheifpandinvCgenes were not expressed underin vitroconditions but were found to be induced in the Peyer's patches of the mouse intestinal tract. In a murine coinfection model, the colonization of the Peyer's patches and the mesenteric lymph nodes of mice by theifp-deficient strain was significantly reduced, and considerably fewer bacteria reached liver and spleen. The absence of InvC did not have a severe influence on bacterial colonization in the murine infection model, and it resulted in only a slightly reduced number ofinvCmutants in the Peyer's patches. The analysis of the host immune response demonstrated that the presence of Ifp and InvC reduced the recruitment of professional phagocytes, especially neutrophils, in the Peyer's patches. These findings support a role for the adhesins in modulating host-pathogen interactions that are important for immune defense.

scholarly journals Aging-Related Impairments to M Cells in Peyer’s Patches Coincide With Disturbances to Paneth Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
David S. Donaldson ◽  
Barbara B. Shih ◽  
Neil A. Mabbott
Keyword(s):  
Cell Differentiation ◽  
Paneth Cell ◽  
The Elderly ◽  
Paneth Cells ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
M Cells ◽  
Aging Effects ◽  
M Cell ◽  
Aged Mice

The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer’s patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer’s patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer’s patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.

scholarly journals Chemokine Requirements for B Cell Entry to Lymph Nodes and Peyer's Patches

2002 ◽  
Vol 196 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Takaharu Okada ◽  
Vu N. Ngo ◽  
Eric H. Ekland ◽  
Reinhold Förster ◽  
Martin Lipp ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Chemokine Receptor ◽  
Cell Entry ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Wild Type ◽  
High Endothelial Venules ◽  
Cell Homing ◽  
T Cell Homing

B cell entry to lymph nodes and Peyer's patches depends on chemokine receptor signaling, but the principal chemokine involved has not been defined. Here we show that the homing of CXCR4−/− B cells is suppressed in CCL19 (ELC)- and CCL21 (SLC)-deficient paucity of lymph node T cells mice, but not in wild-type mice. We also find that CXCR4 can contribute to T cell homing. Using intravital microscopy, we find that B cell adhesion to high endothelial venules (HEVs) is disrupted when CCR7 and CXCR4 are predesensitized. In Peyer's patches, B cell entry is dependent on CXCR5 in addition to CCR7/CXCR4. CXCL12 (SDF1) is displayed broadly on HEVs, whereas CXCL13 (BLC) is found selectively on Peyer's patch follicular HEVs. These findings establish the principal chemokine and chemokine receptor requirements for B cell entry to lymph nodes and Peyer's patches.

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