Murine Innate Immune Response to Virulent Toxigenic and Nontoxigenic Bacillus anthracis Strains
| Autor: | Melissa Drysdale, Gwyneth K. Olson, Mary F. Lipscomb, Theresa M. Koehler, C. Rick Lyons |
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| Rok vydání: | 2007 |
| Předmět: |
Chemokine
Cell Survival Neutrophils Anthrax toxin Bacterial Toxins Immunology Colony Count Microbial Virulence Apoptosis Microbiology Anthrax Mice Immune system Immunity In Situ Nick-End Labeling Animals Host Response and Inflammation Antigens Bacterial Innate immune system biology biology.organism_classification Virology Immunity Innate Bacillus anthracis Mice Inbred C57BL Disease Models Animal Infectious Diseases biology.protein Cytokines Female Parasitology Cytokine secretion Leukocyte Reduction Procedures Spleen |
| Zdroj: | Infection and Immunity. 75:1757-1764 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01712-06 |
| Popis: | Effective treatment of anthrax is hampered by our limited understanding of the pathophysiology of Bacillus anthracis infection. We used a genetically complete (pXO1 + pXO2 + ) virulent B. anthracis strain and four isogenic toxin-null mutants to determine the effects of the anthrax edema toxin (ET; edema factor [EF] plus protective antigen [PA]) and lethal toxin (LT; lethal factor [LF] plus PA) on the host innate response during systemic infection. Using the spleen as an indicator for host response, we found that intravenous inoculation of LT-deficient mutants into C57BL/6 mice significantly increased production of several cytokines over that observed after infection with the parent strain or an EF-deficient mutant. Bacteria producing one or both of the toxins were capable of inducing significant apoptosis of cells present in spleens, whereas apoptosis was greatly reduced in mice infected with nontoxigenic mutants. Mice infected with toxin-producing strains also showed increased splenic neutrophil recruitment compared to mice infected with nontoxigenic strains and neutrophil depletion prior to infection with toxin-producing strains, leading to decreased levels of apoptosis. Together, these studies indicate that anthrax LT suppresses cytokine secretion during infection, but both EF and LF play roles in inducing neutrophil recruitment and enhancing apoptosis. Interestingly, in the absence of LF the effect of EF-induced cell recruitment is further enhanced, perhaps because LF so effectively suppresses the secretion of chemokines. |
| Databáze: | OpenAIRE |
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