دورية أكاديمية
Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague.
| العنوان: | Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague. |
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| المؤلفون: | Olson RM; Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA.; Laboratory for Infectious Disease Research, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA., Dhariwala MO; Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA.; Laboratory for Infectious Disease Research, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA., Mitchell WJ; Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA., Skyberg JA; Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA.; Laboratory for Infectious Disease Research, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA., Anderson DM; Department of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA andersondeb@missouri.edu.; Laboratory for Infectious Disease Research, University of Missouri College of Veterinary Medicine, Columbia, Missouri, USA. |
| المصدر: | Infection and immunity [Infect Immun] 2021 Feb 16; Vol. 89 (3). Date of Electronic Publication: 2021 Feb 16 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| مواضيع طبية MeSH: | Myeloid Differentiation Factor 88/*genetics , Myeloid Differentiation Factor 88/*metabolism , Pigmentation/*genetics , Pigmentation/*physiology , Plague/*genetics , Plague/*metabolism , Yersinia pestis/*genetics , Yersinia pestis/*metabolism, Animals ; Disease Models, Animal ; Gene Expression Regulation, Bacterial ; Humans ; Plague/microbiology |
| مستخلص: | Pneumonic plague, caused by Yersinia pestis , is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of Y. pestis , inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection. We previously showed that Y. pestis lacking the 102-kb chromosomal pigmentation locus ( pgm ) is unable to cause inflammatory damage in the lungs, whereas the wild-type (WT) strain induces the toxic MyD88 pulmonary inflammatory response. In this work, we investigated the involvement of the pgm in skewing the inflammatory response during pneumonic plague. We show that the early MyD88-dependent and -independent cytokine responses to pgm - Y. pestis infection of the lungs are similar yet distinct from those that occur during pgm + infection. Furthermore, we found that MyD88 was necessary to prevent growth of the iron-starved pgm - Y. pestis despite the presence of iron chelators lactoferrin and transferrin. However, while this induced neutrophil recruitment, there was no hyperinflammatory response, and pulmonary disease was mild without MyD88. In contrast, growth in blood and tissues progressed rapidly in the absence of MyD88, due to an almost total loss of serum interferon gamma (IFN-γ). We further show that the expression of MyD88 by myeloid cells is important to control bacteremia but not the primary lung infection. The combined data indicate distinct roles for myeloid and nonmyeloid MyD88 and suggest that expression of the pgm is necessary to skew the inflammatory response in the lungs to cause pneumonic plague. (Copyright © 2021 American Society for Microbiology.) |
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| معلومات مُعتمدة: | R01 AI129996 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: MyD88; Yersinia pestis; immunopathology; inflammation; interferon gamma; pigmentation locus; plague; pneumonic plague; septicemic plague |
| المشرفين على المادة: | 0 (Myeloid Differentiation Factor 88) |
| تواريخ الأحداث: | Date Created: 20201201 Date Completed: 20210722 Latest Revision: 20210817 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8097263 |
| DOI: | 10.1128/IAI.00595-20 |
| PMID: | 33257532 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5522 |
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| DOI: | 10.1128/IAI.00595-20 |