Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice

Roux, Christelle M.; Rolán, Hortensia G.; Santos, Renato L.; Beremand, Phillip D.; Thomas, Terry L.; Adams, L. Garry; Tsolis, Renée M.

doi:10.1111/j.1462-5822.2007.00922.x

Cited by 120 publications

(102 citation statements)

References 96 publications

(112 reference statements)

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“…Several other intracellular bacterial pathogens, including Francisella tularensis, Mycobacterium tuberculosis, Legionella pneumophila, and Brucella spp., activate a similar host immune response. In each case, induction of this host pathway requires live bacteria, and in the latter three cases it is associated with auxiliary secretion systems (10,28,32,33). These data suggest that bacterial auxiliary secretion systems, including MDRs, are necessary to trigger the host cytosolic surveillance pathway.…”

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confidence: 89%

Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway

Crimmins¹,

Schelle²,

Herskovits³

et al. 2009

Infect Immun

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Infection with wild-type Listeria monocytogenes activates a host cytosolic surveillance response characterized by the expression of beta interferon (IFN-␤). We performed a genetic screen to identify L. monocytogenes transposon insertion mutants that induced altered levels of host IFN-␤ expression. One mutant from this screen induced elevated levels of IFN-␤ and harbored a Tn917 insertion upstream of lmo0558. This study identified lmo0558 as the 6-phosphogluconolactonase gene (pgl), which encodes the second enzyme in the pentose phosphate pathway. pgl mutant L. monocytogenes accumulated and secreted large amounts of gluconate, likely derived from labile 6-phosphogluconolactone, the substrate of Pgl. The pgl deletion mutant had decreased growth in glucose-limiting minimal medium but grew normally when excess glucose was added. Microarray analysis revealed that the pgl deletion mutant had increased expression of several ␤-glucosidases, consistent with known inhibition of ␤-glucosidases by 6-phosphogluconolactone. While growth in macrophages was indistinguishable from that of wild-type bacteria, pgl mutant L. monocytogenes exhibited a 15-to 30-fold defect in growth in vivo. In addition, L. monocytogenes harboring an in-frame deletion of pgl was more sensitive to oxidative stress. This study identified L. monocytogenes pgl and provided the first link between the bacterial pentose phosphate pathway and activation of host IFN-␤ expression.Listeria monocytogenes is a gram-positive, food-borne facultative intracellular pathogen that causes invasive, life-threatening infections, mainly in pregnant women, newborns, the elderly, and the immunosuppressed (39). In addition, L. monocytogenes has been studied for decades as a model pathogen, illuminating many aspects of host-pathogen interaction. The cell biology of its intracellular life cycle has been particularly well characterized. After phagocytosis by a macrophage, L. monocytogenes rapidly escapes from the phagosome into the cytosol, an event mediated by the pore-forming cytolysin listeriolysin O (29). L. monocytogenes is well adapted to its cytosolic niche, possessing virulence factors that allow utilization of cytosolic sugar sources and polymerization of host actin to move from cell to cell (4, 25). It is evident that L. monocytogenes has evolved specific mechanisms to grow in the host cytosol; however, the presence of cytosolic L. monocytogenes triggers a host innate immune response. Upon entry of L. monocytogenes into cells, a host cell cytosolic surveillance pathway is activated, including a transcriptional program that leads to the robust expression of beta interferon (IFN-␤) (19,22,23,34). However, the host and bacterial components responsible for the activation of the cytosolic surveillance pathway remain largely unknown.Our lab previously performed a genetic screen to identify L. monocytogenes transposon insertion mutants that induced enhanced or diminished activation of the host cytosolic surveillance system (6). We found that bacterial multidrug resistance tra...

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confidence: 89%

Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway

Crimmins¹,

Schelle²,

Herskovits³

et al. 2009

Infect Immun

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“…Real-time PCR was performed for each cDNA sample (5 l per reaction) in duplicate using the 7900HT fast real-time PCR system. For the mouse experiments, primers for mouse glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (66), mouse IL-17A (57), mouse IL-22 (27), mouse gamma interferon (IFN-␥) (57), mouse tumor necrosis factor alpha (TNF-␣) (83), mouse lipocalin 2 (62), regenerating islet-derived 3 gamma (Reg3␥) (27), and Reg3␤ (77) were used. Results were analyzed using the comparative Ct method and by normalizing the data to GAPDH.…”

Section: Methodsmentioning

confidence: 99%

Microbial Amyloids Induce Interleukin 17A (IL-17A) and IL-22 Responses via Toll-Like Receptor 2 Activation in the Intestinal Mucosa

et al. 2012

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The Toll-like receptor 2 (TLR2)/TLR1 receptor complex responds to amyloid fibrils, a common component of biofilm material produced by members of the phyla Firmicutes, Bacteroidetes, and Proteobacteria. To determine whether this TLR2/TLR1 ligand stimulates inflammatory responses when bacteria enter intestinal tissue, we investigated whether expression of curli amyloid fibrils by the invasive enteric pathogen Salmonella enterica serotype Typhimurium contributes to T helper 1 and T helper 17 responses by measuring cytokine production in the mouse colitis model. A csgBA mutant, deficient in curli production, elicited decreased expression of interleukin 17A (IL-17A) and IL-22 in the cecal mucosa compared to the S. Typhimurium wild type. In TLR2-deficient mice, IL-17A and IL-22 expression was blunted during S. Typhimurium infection, suggesting that activation of the TLR2 signaling pathway contributes to the expression of these cytokines. T cells incubated with supernatants from bone marrow-derived dendritic cells (BMDCs) treated with curli fibrils released IL-17A in a TLR2-dependent manner in vitro. Lower levels of IL-6 and IL-23 production were detected in the supernatants of the TLR2-deficient BMDCs treated with curli fibrils. Consistent with this, three distinct T-cell populations-CD4؉ T helper cells, cytotoxic CD8 ؉ T cells, and ␥␦ T cells-produced IL-17A in response to curli fibrils in the intestinal mucosa during S. Typhimurium infection. Notably, decreased IL-6 expression by the dendritic cells and decreased IL-23 expression by the dendritic cells and macrophages were observed in the cecal mucosa of mice infected with the curli mutant. We conclude that TLR2 recognition of bacterial amyloid fibrils in the intestinal mucosa represents a novel mechanism of immunoregulation, which contributes to the generation of inflammatory responses, including production of IL-17A and IL-22, in response to bacterial entry into the intestinal mucosa.

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“…The extraction of total RNA from the spleen with TRIzol reagent (Invitrogen, Carlsbad, CA) was performed as described previously (49). For a quantitative analysis of mRNA levels, 500 ng of total RNA from each sample was reverse transcribed in a 50-l volume (TaqMan reverse transcription [RT] reagent; Applied Biosystems), and 4 l of cDNA was used for each real-time reaction.…”

Section: Methodsmentioning

confidence: 99%

Both Hemolytic Anemia and Malaria Parasite-Specific Factors Increase Susceptibility to NontyphoidalSalmonella entericaSerovar Typhimurium Infection in Mice

Roux¹,

Butler²,

Chau³

et al. 2010

Infect Immun

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Severe pediatric malaria is an important risk factor for developing disseminated infections with nontyphoidal Salmonella serotypes (NTS). While recent animal studies on this subject are lacking, early work suggests that an increased risk for developing systemic NTS infection during malaria is caused by hemolytic anemia, which leads to reduced macrophage microbicidal activity. Here we established a model for oral Salmonella enterica serotype Typhimurium challenge in mice infected with Plasmodium yoelii nigeriensis. Initial characterization of this model showed that 5 days after coinoculation, P. yoelii nigeriensis infection increased the recovery of S. Typhimurium from liver and spleen by approximately 1,000-fold. The increased bacterial burden could be only partially recapitulated by antibody-mediated hemolysis, which increased the recovery of S. Typhimurium from liver and spleen by 10-fold. These data suggested that both hemolysis and P. yoelii nigeriensis-specific factors contributed to the increased susceptibility to S. Typhimurium. The mechanism by which hemolysis impaired resistance to S. Typhimurium was further investigated. In vitro, S. Typhimurium was recovered 24 h after infection of hemophagocytic macrophages in 2-fold-higher numbers than after infection of mock-treated macrophages, making it unlikely that reduced macrophage microbicidal activity was solely responsible for hemolysis-induced immunosuppression during malaria. Infection with P. yoelii nigeriensis, but not antibodymediated hemolysis, reduced serum levels of interleukin-12p70 (IL-12p70) in response to S. Typhimurium challenge. Collectively, studies establishing a mouse model for this coinfection suggest that multiple distinct malaria-induced immune defects contribute to increased susceptibility to S. Typhimurium.

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Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice

Cited by 120 publications

References 96 publications

Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway

Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway

Microbial Amyloids Induce Interleukin 17A (IL-17A) and IL-22 Responses via Toll-Like Receptor 2 Activation in the Intestinal Mucosa

Both Hemolytic Anemia and Malaria Parasite-Specific Factors Increase Susceptibility to NontyphoidalSalmonella entericaSerovar Typhimurium Infection in Mice

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