0379756 - BC 2013 RIV US eng J - Článek v odborném periodiku
Chen, G. - Severo, M. S. - Sakhon, O. S. - Choy, A. - Herron, M. J. - Felsheim, R. F. - Wiryawan, H. - Liao, J. - Johns, J. L. - Munderloh, U. G. - Sutterwala, F. S. - Kotsyfakis, Michalis - Pedra, J. H. F.
Anaplasma phagocytophilum Dihydrolipoamide Dehydrogenase 1 Affects Host-Derived Immunopathology during Microbial Colonization.
Infection and Immunity. Roč. 80, č. 9 (2012), s. 3194-3205. ISSN 0019-9567. E-ISSN 1098-5522
Institucionální podpora: RVO:60077344
Klíčová slova: ricketsia * microbial colonization * immunopathology * inflammation * signaling pathways
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.074, rok: 2012 ; AIS: 1.312, rok: 2012
Web výsledku:
http://iai.asm.org/content/80/9/3194DOI: https://doi.org/10.1128/IAI.00532-12

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.
Trvalý link: http://hdl.handle.net/11104/0210640