14 results on '"Okamoto, Sharon"'
Search Results
2. Salmonella-induced Diarrhea Occurs in the Absence of IL-8 Receptor (CXCR2)-Dependent Neutrophilic Inflammation
- Author
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Marchelletta, Ronald R., Gareau, Melanie G., Okamoto, Sharon, Guiney, Donald G., Barrett, Kim E., and Fierer, Joshua
- Published
- 2015
3. Altered Expression and Localization of Ion Transporters Contribute to Diarrhea in Mice With Salmonella-Induced Enteritis
- Author
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Marchelletta, Ronald R., Gareau, Melanie G., McCole, Declan F., Okamoto, Sharon, Roel, Elise, Klinkenberg, Rachel, Guiney, Donald G., Fierer, Joshua, and Barrett, Kim E.
- Published
- 2013
- Full Text
- View/download PDF
4. Vaccination with Irradiated Listeria Induces Protective T Cell Immunity
- Author
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Datta, Sandip K., Okamoto, Sharon, Hayashi, Tomoko, Shin, Samuel S., Mihajlov, Ivan, Fermin, Agnes, Guiney, Donald G., Fierer, Joshua, and Raz, Eyal
- Published
- 2006
- Full Text
- View/download PDF
5. Myeloid differentiation factor 88 (MyD88) and IL-1R1 signaling contribute to resistance to Coccidioides immitis
- Author
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Viriyakosol, Suganya, Walls, Lorraine, Okamoto, Sharon, Raz, Eyal, Williams, David L, and Fierer, Joshua
- Subjects
Medicine and Health Sciences - Abstract
Rodents are a natural host for the dimorphic pathogenic fungi Coccidioides immitis and posadasii, and mice are a good model for human infection. Humans and rodents both express Dectin-1 and TLR2 on myeloid cells and those receptors collaborate to maximize the cytokine/chemokine responses to spherules (the tissue form of the fungi), and to formalin killed spherules (FKS). We showed that Dectin-1 is necessary for resistance to pulmonary coccidioidomycosis, but the importance of TLR2 in vivo is uncertain. MyD88 is the adapter protein for TLR2 and 4, and IL-1R1 and IL-18R1. MyD88/TRIF -/-and MyD88 -/- mice were equally susceptible to C. immitis infection, compared to C57BL/6 (B6) controls. Of the four surface receptors, only IL-1R1 was required for resistance to C. immitis, partially explaining the susceptibility of MyD88 -/- mice. We also found that FKS stimulated production of IL-1Ra by BMDC, independent of MyD88 and Dectin-1. There also was a very high concentration of IL-1Ra in the lungs of infected B6 mice, supporting the potential importance of this regulatory IL-1 family protein in the largely ineffective response of B6 mice to coccidioidomycosis. These results suggest that IL-1R1 signaling is important for defense against C. immitis infection.
- Published
- 2018
6. 754 Altered Expression and Localization of Colonic Ion Transporters in a Mouse Model of Salmonella-Induced Diarrhea
- Author
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Marchelletta, Ronald R., McCole, Declan F., Okamoto, Sharon, Roel, Elise, Klinkenberg, Rachel, Guiney, Donald, Fierer, Joshua, and Barrett, Kim E.
- Published
- 2012
- Full Text
- View/download PDF
7. A Model of Salmonella Colitis with Features of Diarrhea in SLC11A1 Wild-Type Mice.
- Author
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Heungjeong Woo, Okamoto, Sharon, Guiney, Donald, Gunn, John S., and Fierer, Joshua
- Subjects
- *
COLITIS diagnosis , *DIARRHEA , *MICROBIAL virulence , *PATHOGENIC microorganisms , *GENETIC mutation , *LABORATORY mice ,SALMONELLA genetics - Abstract
Background: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1G169D allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1G169) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10-14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPH-deficient (gp91phox) mice. However, strain 14028s caused severe colitis and diarrhea in gp91phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. Conclusions: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore, a Salmonella phoP mutant can be cleared from the colon by non-oxidative host defenses. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
8. Identification of Salmonella SPI-2 secretion system components required for SpvB-mediated cytotoxicity in macrophages and virulence in mice.
- Author
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Browne, Sara H., Hasegawa, Patricia, Okamoto, Sharon, Fierer, Joshua, and Guiney, Donald G.
- Subjects
SALMONELLA ,CELL-mediated cytotoxicity ,LABORATORY mice ,INTRACELLULAR pathogens ,ACTIN ,TOXINS ,ENTEROBACTERIACEAE ,MACROPHAGE activation ,MICROBIAL virulence ,PATHOGENIC microorganisms - Abstract
The Salmonella SpvB protein possesses ADP-ribosyl transferase activity. SpvB, acting as an intracellular toxin, covalently modifies monomeric actin, leading to loss of F-actin filaments in Salmonella-infected human macrophages. Using defined Salmonella mutants, different functional components of the SPI-2 type three secretion system (TTSS), ssaV, spiC, sseB, sseC, and sseD, were found to be required for SpvB-mediated actin depolymerization in human macrophages. Expression of SpvB protein in Salmonella was not affected by any of the SPI-2 mutants and the effects of these loci were not due to reduced numbers of intracellular bacteria. Interestingly, the major SPI-2 virulence effector, SifA, is not required for SpvB action. Further, caspase-3 activation is an additional marker of cytotoxicity in Salmonella-infected human macrophages. Caspase-3 activity depended on SpvB and SPI-2 TTSS function, but not on SifA. These human macrophage cell culture results were corroborated by virulence studies in mice. Using competitive infection of mice with mixed inocula of single and double mutants, spvBmut1 mutation did not have an effect independent of ssaJ mutation, essential for SPI-2 TTSS function. In contrast, competitive infection studies in mice confirmed that SpvB and SifA have independent virulence effects, as predicted by the macrophage studies. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
9. Intestinal Transport Defects in a Mouse Model of Salmonella-Induced Diarrhea
- Author
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Marchelletta, Ronald, McCole, Declan F., Okamoto, Sharon, Roel, Elise, Klinkenberg, Rachel, Guiney, Donald, Fierer, Joshua, and Barrett, Kim E.
- Published
- 2011
- Full Text
- View/download PDF
10. Interleukin-8 Receptor 2 (IL-8R2)-Deficient Mice Are More Resistant to Pulmonary Coccidioidomycosis than Control Mice.
- Author
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Carlin AF, Viriyakosol S, Okamoto S, Walls L, and Fierer J
- Subjects
- Animals, Biomarkers, Coccidioidomycosis metabolism, Coccidioidomycosis pathology, Cytokines metabolism, Disease Models, Animal, Genetic Predisposition to Disease, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Interferon-gamma metabolism, Leukocyte Count, Mice, Mice, Knockout, Neutrophils immunology, Neutrophils metabolism, Pneumonia metabolism, Pneumonia pathology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Transcriptome, Coccidioides immunology, Coccidioidomycosis etiology, Disease Susceptibility, Pneumonia etiology, Receptors, Interleukin-8B deficiency
- Abstract
The pathology of human coccidioidomycosis is granulomatous inflammation with many neutrophils surrounding ruptured spherules, but the chemotactic pathways that draw neutrophils into the infected tissues are not known. We previously showed that formalin-killed spherules (FKS) stimulate mouse macrophages to secret macrophage inflammatory protein 2 (MIP-2), which suggested that CXC ELR+ chemokines might be involved in neutrophil recruitment in vivo To test that hypothesis, we intranasally infected interleukin-8R2 (IL-8R2) ( Cxcr2 )-deficient mice on a BALB/c background with Coccidioides immitis RS. IL-8R2-deficient mice had fewer neutrophils in infected lungs than controls, but unexpectedly the IL-8R2-deficient mice had fewer organisms in their lungs than the control mice. Infected IL-8R2-deficient mouse lungs had higher expression of genes associated with lymphocyte activation, including the Th1 and Th17-related cytokines Ifnγ and Il17a and the transcription factors Stat1 and Rorc Additionally, bronchial alveolar lavage fluid from infected IL-8R2-deficient mice contained more IL-17A and interferon-γ (IFN-γ). We postulate that neutrophils in the lung directly or indirectly interfere with the development of a protective Th1/Th17 immune response to C. immitis at the site of infection., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
- Full Text
- View/download PDF
11. APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia.
- Author
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Viriyakosol S, Kapoor M, Okamoto S, Covel J, Soltow QA, Trzoss M, Shaw KJ, and Fierer J
- Subjects
- Amphotericin B therapeutic use, Animals, Coccidioides drug effects, Disease Models, Animal, Female, Fluconazole therapeutic use, Mice, Mice, Inbred C57BL, Microbial Sensitivity Tests, Prodrugs therapeutic use, Triazoles therapeutic use, Aminopyridines therapeutic use, Antifungal Agents therapeutic use, Coccidioides pathogenicity, Isoxazoles therapeutic use, Pneumonia drug therapy
- Abstract
Coccidioidomycosis is a systemic fungal infection caused by the inhalation of the arthroconidia of either of two closely related dimorphic fungi, Coccidioides immitis and C. posadasii , that are endemic in the southwestern United States and other areas in the Western Hemisphere. Chronic cavitary pulmonary infections and extrapulmonary sites of infection are very difficult to treat and often require lifelong azole therapy. APX001A is the first in a new class of broad-spectrum antifungal agents that inhibit Gwt1, an enzyme which is required for cell wall localization of glycosylphosphatidylinositol (GPI)-anchored mannoproteins in fungi. APX001A and several analogs were highly active against clinical isolates of Coccidioides , inhibiting hyphal growth at low nanogram/ml concentrations. APX001 is the N-phosphonooxymethyl prodrug of APX001A, currently in clinical trials for the treatment of invasive fungal infections. Mice were treated orally once daily with 26 mg/kg/day of APX001 and the prodrug analog APX2097, 2 h after administration of the pan-cytochrome P450 inhibitor 1-aminobenzotriazole, which was used to enhance drug half-life and exposures to more closely mimic human pharmacokinetics of APX001A. Five days of treatment reduced lung colony counts by nearly 3 logs and prevented dissemination, similar to the efficacy of fluconazole dosed orally at 25 mg/kg twice daily. In a survival experiment, both APX001- and APX2097-treated mice survived significantly longer than control and fluconazole-treated mice. APX001 and other members of this new class of antifungal agents may offer great promise as effective therapies for coccidioidomycosis., (Copyright © 2019 Viriyakosol et al.)
- Published
- 2019
- Full Text
- View/download PDF
12. Myeloid Differentiation Factor 88 and Interleukin-1R1 Signaling Contribute to Resistance to Coccidioides immitis.
- Author
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Viriyakosol S, Walls L, Okamoto S, Raz E, Williams DL, and Fierer J
- Subjects
- Animals, Dendritic Cells, Lectins, C-Type genetics, Lectins, C-Type metabolism, Macrophages, Peritoneal metabolism, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 genetics, Receptors, Interleukin-1 Type I genetics, Toll-Like Receptor 2 genetics, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Coccidioides immunology, Coccidioidomycosis immunology, Myeloid Differentiation Factor 88 metabolism, Receptors, Interleukin-1 Type I metabolism
- Abstract
Rodents are a natural host for the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadasii , and mice are a good model for human infection. Humans and rodents both express Dectin-1 and Toll-like receptor 2 (TLR2) on myeloid cells, and those receptors collaborate to maximize the cytokine/chemokine responses to spherules (the tissue form of the fungi) and to formalin-killed spherules (FKS). We showed that Dectin-1 is necessary for resistance to pulmonary coccidioidomycosis, but the importance of TLR2 in vivo is uncertain. Myeloid differentiation factor 88 (MyD88) is the adapter protein for TLR2 and -4, interleukin-1R1 (IL-1R1), and IL-18R1. MyD88/TRIF
-/- and MyD88-/- mice were equally susceptible to C. immitis infection, in contrast to C57BL/6 (B6) controls. Of the four surface receptors, only IL-1R1 was required for resistance to C. immitis , partially explaining the susceptibility of MyD88-/- mice. We also found that FKS stimulated production of IL-1Ra by bone marrow-derived dendritic cells (BMDCs), independent of MyD88 and Dectin-1. There also was a very high concentration of IL-1Ra in the lungs of infected B6 mice, supporting the potential importance of this regulatory IL-1 family protein in the largely ineffective response of B6 mice to coccidioidomycosis. These results suggest that IL-1R1 signaling is important for defense against C. immitis infection., (Copyright © 2018 American Society for Microbiology.)- Published
- 2018
- Full Text
- View/download PDF
13. Diarrhea and colitis in mice require the Salmonella pathogenicity island 2-encoded secretion function but not SifA or Spv effectors.
- Author
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Fierer J, Okamoto S, Banerjee A, and Guiney DG
- Subjects
- ADP Ribose Transferases genetics, ADP Ribose Transferases metabolism, Alleles, Animals, Bacterial Proteins genetics, Cation Transport Proteins genetics, Cation Transport Proteins metabolism, Colon pathology, Feces chemistry, Female, Genetic Predisposition to Disease, Glycoproteins genetics, Glycoproteins metabolism, Macrophages physiology, Membrane Proteins genetics, Mice, Mice, Inbred BALB C, Salmonella genetics, Salmonella metabolism, Salmonella pathogenicity, Salmonella typhimurium metabolism, Salmonella typhimurium pathogenicity, Specific Pathogen-Free Organisms, Virulence genetics, Virulence Factors genetics, Virulence Factors metabolism, Bacterial Proteins metabolism, Colitis microbiology, Diarrhea microbiology, Membrane Proteins metabolism, Salmonella Infections, Animal microbiology, Salmonella typhimurium genetics
- Abstract
We investigated the roles of Salmonella pathogenicity island 2 (SPI-2) and two SPI-2 effectors in Salmonella colitis and diarrhea in genetically resistant BALB/c.D2(Slc11a1) congenic mice with the wild-type Nramp1 locus. Wild-type Salmonella enterica serovar Typhimurium 14028s caused a pan-colitis, and the infected mice developed frank diarrhea with a doubling of the fecal water content. An ssaV mutant caused only a 26% increase in fecal water content, without producing the pathological changes of colitis, and it did not cause weight loss over a 1-week period of observation. However, two SPI-2 effector mutants, the spvB and sifA mutants, and a double spvB sifA mutant caused diarrhea and colitis, even though the sifA mutant was sensitive to killing by bone marrow-derived macrophages from BALB/c.D2 mice and was severely impaired in extraintestinal growth but not in growth in the cecum. These results demonstrate that systemic S. enterica infection and diarrhea/colitis are distinct pathogenic processes and that only the former requires spvB and sifA.
- Published
- 2012
- Full Text
- View/download PDF
14. A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice.
- Author
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Woo H, Okamoto S, Guiney D, Gunn JS, and Fierer J
- Subjects
- Animals, Cation Transport Proteins, Colitis pathology, Colon microbiology, Disease Susceptibility, Kanamycin, Membrane Glycoproteins deficiency, Mice, NADPH Oxidase 2, NADPH Oxidases deficiency, Salmonella typhimurium genetics, Colitis microbiology, Diarrhea etiology, Disease Models, Animal, Salmonella Infections, Animal, Salmonella typhimurium pathogenicity
- Abstract
Background: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1(G169D) allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1(G169)) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2(Nramp1) congenic started losing weight 5 days post-infection and they began to die from colitis 10-14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPH-deficient (gp91(phox)) mice. However, strain 14028s caused severe colitis and diarrhea in gp91(phox)-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis., Conclusions: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore, a Salmonella phoP mutant can be cleared from the colon by non-oxidative host defenses.
- Published
- 2008
- Full Text
- View/download PDF
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