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Anaplasma phagocytophilum Dihydrolipoamide Dehydrogenase 1 Affects Host-Derived Immunopathology during Microbial Colonization
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SYSNO ASEP 0379756 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Anaplasma phagocytophilum Dihydrolipoamide Dehydrogenase 1 Affects Host-Derived Immunopathology during Microbial Colonization Author(s) Chen, G. (US)
Severo, M. S. (US)
Sakhon, O. S. (US)
Choy, A. (US)
Herron, M. J. (US)
Felsheim, R. F. (US)
Wiryawan, H. (US)
Liao, J. (US)
Johns, J. L. (US)
Munderloh, U. G. (US)
Sutterwala, F. S. (US)
Kotsyfakis, Michalis (BC-A) RID, ORCID
Pedra, J. H. F. (US)Source Title Infection and Immunity. - : American Society for Microbiology - ISSN 0019-9567
Roč. 80, č. 9 (2012), s. 3194-3205Number of pages 12 s. Language eng - English Country US - United States Keywords ricketsia ; microbial colonization ; immunopathology ; inflammation ; signaling pathways Subject RIV EB - Genetics ; Molecular Biology Institutional support BC-A - RVO:60077344 UT WOS 000307869100021 DOI https://doi.org/10.1128/IAI.00532-12 Annotation Anaplasma phagocytophilum is a tick-borne rickettsial pathogen that provokes an acute inflammatory response during mammalian infection. The illness caused by A. phagocytophilum, human granulocytic anaplasmosis, occurs irrespective of pathogen load and results instead from host-derived immunopathology. Thus, characterizing A. phagocytophilum genes that affect the inflammatory process is critical for understanding disease etiology. By using an A. phagocytophilum Himar1 transposon mutant library, we showed that a single transposon insertion into the A. phagocytophilum dihydrolipoamide dehydrogenase 1 gene (lpda1 [APH_0065]) affects inflammation during infection. A. phagocytophilum lacking lpda1 revealed enlargement of the spleen, increased splenic extramedullary hematopoiesis, and altered clinicopathological abnormalities during mammalian colonization. Furthermore, LPDA1-derived immunopathology was independent of neutrophil infection and correlated with enhanced reactive oxygen species from NADPH oxidase and nuclear factor (NF)-κB signaling in macrophages. Taken together, these findings suggest the presence of different signaling pathways in neutrophils and macrophages during A. phagocytophilum invasion and highlight the importance of LPDA1 as an immunopathological molecule. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2013 Electronic address http://iai.asm.org/content/80/9/3194
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