7 results on '"Zimmerman, Lindsey I"'
Search Results
2. Lack of Lipid A Pyrophosphorylation and Functional lptA Reduces Inflammation by Neisseria Commensals
- Author
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John, Constance M, Liu, Mingfeng, Phillips, Nancy J, Yang, Zhijie, Funk, Courtney R, Zimmerman, Lindsey I, Griffiss, J McLeod, Stein, Daniel C, and Jarvis, Gary A
- Subjects
Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Blotting ,Southern ,Cells ,Cultured ,Computational Biology ,Humans ,Inflammation ,Lipid A ,Neisseria ,Phosphorylation ,Signal Transduction ,Tandem Mass Spectrometry ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Immunology ,Medical microbiology - Abstract
The interaction of the immune system with Neisseria commensals remains poorly understood. We have previously shown that phosphoethanolamine on the lipid A portion of lipooligosaccharide (LOS) plays an important role in Toll-like receptor 4 (TLR4) signaling. For pathogenic Neisseria, phosphoethanolamine is added to lipid A by the phosphoethanolamine transferase specific for lipid A, which is encoded by lptA. Here, we report that Southern hybridizations and bioinformatics analyses of genomic sequences from all eight commensal Neisseria species confirmed that lptA was absent in 15 of 17 strains examined but was present in N. lactamica. Mass spectrometry of lipid A and intact LOS revealed the lack of both pyrophosphorylation and phosphoethanolaminylation in lipid A of commensal species lacking lptA. Inflammatory signaling in human THP-1 monocytic cells was much greater with pathogenic than with commensal Neisseria strains that lacked lptA, and greater sensitivity to polymyxin B was consistent with the absence of phosphoethanolamine. Unlike the other commensals, whole bacteria of two N. lactamica commensal strains had low inflammatory potential, whereas their lipid A had high-level pyrophosphorylation and phosphoethanolaminylation and induced high-level inflammatory signaling, supporting previous studies indicating that this species uses mechanisms other than altering lipid A to support commensalism. A meningococcal lptA deletion mutant had reduced inflammatory potential, further illustrating the importance of lipid A pyrophosphorylation and phosphoethanolaminylation in the bioactivity of LOS. Overall, our results indicate that lack of pyrophosphorylation and phosphoethanolaminylation of lipid A contributes to the immune privilege of most commensal Neisseria strains by reducing the inflammatory potential of LOS.
- Published
- 2012
3. Maternal and Neonatal Vaccination Protects Newborn Baboons From Pertussis Infection
- Author
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Warfel, Jason M., Papin, James F., Wolf, Roman F., Zimmerman, Lindsey I., and Merkel, Tod J.
- Published
- 2014
4. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model
- Author
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Warfel, Jason M., Zimmerman, Lindsey I., and Merkel, Tod J.
- Published
- 2014
5. Construction and Characterization of a Derivative of Neisseria gonorrhoeae Strain MS11 Devoid of All opa Genes.
- Author
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LeVan, Adriana, Zimmerman, Lindsey I., Mahle, Amanda C., Swanson, Karen V., DeShong, Philip, Park, Juhee, Edwards, Vonetta L., Wenxia Song, and Stein, Daniel C.
- Subjects
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NEISSERIA gonorrhoeae , *CYTOMETRY , *CELLS , *CELL communication , *MONOCLONAL antibodies - Abstract
To better understand the role of Opa in gonococcal infections, we created and characterized a derivative of MS11 (MS11Δopa) that had the coding sequence for all 11 Opa proteins deleted. The MS11Δopa bacterium lost the ability to bind to purified lipoo-ligosaccharide (LOS). While nonpiliated MS11Δopa and nonpiliated Opa-expressing MS11 cells grew at the same rate, nonpiliated MS11Δopa cells rarely formed clumps of more than four bacteria when grown in broth with vigorous shaking. Using flow cytometry analysis, we demonstrated that MS11Δopa produced a homogeneous population of bacteria that failed to bind monoclonal antibody (MAb) 4B 12, a MAb specific for Opa. Opa-expressing MS11 cells consisted of two predominant populations, where ~ 85% bound MAb 4B 12 to a significant level and the other population bound little if any MAb. Approximately 90% of bacteria isolated from a phenotypically Opa-negative colony (a colony that does not refract light) failed to bind MAb 4B12; the remaining 10% bound MAb to various degrees. Piliated MS11Δopa cells formed dispersed microcolonies on ME180 cells which were visually distinct from those of piliated Opa-expressing MS11 cells. When Opa expression was reintroduced into MS11Δopa, the adherence ability of the strain recovered to wild-type levels. These data indicate that Opa contributes to both bacterium-bacterium and bacterium-host cell interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
6. Histopathology of Bordetella pertussis in the Baboon Model.
- Author
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Zimmerman LI, Papin JF, Warfel J, Wolf RF, Kosanke SD, and Merkel TJ
- Subjects
- Animals, Disease Models, Animal, Histocytochemistry, Immunohistochemistry, Papio, Trachea pathology, Bordetella pertussis growth & development, Lung pathology, Whooping Cough pathology
- Abstract
Pertussis is a severe respiratory disease caused by Bordetella pertussis The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model., (Copyright © 2018 American Society for Microbiology.)
- Published
- 2018
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7. Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis.
- Author
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Warfel JM, Zimmerman LI, and Merkel TJ
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- Animals, Bacterial Load, Bordetella pertussis immunology, Diphtheria-Tetanus-Pertussis Vaccine administration & dosage, Disease Models, Animal, Humans, Interleukin-17 genetics, Nasopharynx microbiology, Papio, Pertussis Vaccine administration & dosage, Pertussis Vaccine standards, Transcription, Genetic, United States, Vaccines, Acellular administration & dosage, Vaccines, Acellular immunology, Vaccines, Acellular standards, Whooping Cough transmission, Diphtheria-Tetanus-Pertussis Vaccine immunology, Pertussis Vaccine immunology, Whooping Cough immunology
- Abstract
Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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