| Innate immunity against Granulibacter bethesdensis, an emerging Gram-negative bacterial pathogen. | |
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MedLine Citation:
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PMID: 22184421 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Acetic acid bacteria were previously considered non-pathogenic in humans. However, over the past decade, five genera of Acetobacteraceae have been isolated from patients with inborn or iatrogenic immunodeficiencies. Here, we describe the first studies of the interactions of the human innate immune system with a member of this bacterial family, Granulibacter bethesdensis, an emerging pathogen in patients with chronic granulomatous disease (CGD). Efficient phagocytosis of G. bethesdensis by normal and CGD polymorphonuclear leukocytes (PMN) required heat-labile serum components (e.g., C3) and binding of C3 and C9 to G. bethesdensis was detected by immunoblotting. However, this organism survived in human serum concentrations ≥90% indicating a high degree of serum resistance. Consistent with the clinical host tropism of G. bethesdensis, CGD PMN were unable to kill this organism while normal PMN, in the presence of serum, reduced colony-forming units by about 50% after 24-h co-culture. This finding, together with the observations that G. bethesdensis was sensitive to H(2)O(2) but resistant to LL-37, a human cationic antimicrobial peptide, suggest an inherent resistance to O(2)-independent killing. Interestingly, 10-100 times greater numbers of G. bethesdensis were required to achieve the same level of ROS production induced by E.coli in normal PMN. In addition to the relative inability of the organism to elicit production of PMN ROS, G.bethesdensis inhibited both constitutive and FAS-induced PMN apoptosis. These properties of reduced PMN activation and resistance to non-oxidative killing mechanisms likely play an important role in G. bethesdensis pathogenesis. |
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Authors:
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Kol A Zarember; Kimberly R Marshall-Batty; Anna R Cruz; Jessica Chu; Michael E Fenster; Adam R Shoffner; Larissa S Rogge; Adeline R Whitney; Meggan Czapiga; Helen H Song; Pamela A Shaw; Kunio Nagashima; Harry L Malech; Frank R Deleo; Steven M Holland; John I Gallin; David E Greenberg |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-19 |
Journal Detail:
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Title: Infection and immunity Volume: - ISSN: 1098-5522 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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