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Anaplasma phagocytophilum Dihydrolipoamide Dehydrogenase 1 Affects Host-Derived Immunopathology during Microbial Colonization
- Source :
- Infection and immunity, vol 80, iss 9
- Publication Year :
- 2012
- Publisher :
- American Society for Microbiology, 2012.
-
Abstract
- 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.
- Subjects :
- Neutrophils
immunology [Dihydrolipoamide Dehydrogenase]
animal diseases
Inbred C57BL
immunology
Mice
Immunopathology
pathogenicity
Pathogen
immunology [Neutrophils]
NADPH oxidase
biology
immunology [Virulence Factors]
Bacterial Infections
immunology [Macrophages]
microbiology [Spleen]
Infectious Diseases
medicine.anatomical_structure
Female
immunology [Ehrlichiosis]
medicine.symptom
Anaplasma phagocytophilum
Adult
Human granulocytic anaplasmosis
Virulence Factors
Immunology
Spleen
Inflammation
Microbiology
Insertional
parasitic diseases
medicine
Animals
Humans
Dihydrolipoamide Dehydrogenase
Dihydrolipoamide dehydrogenase
Macrophages
microbiology
Ehrlichiosis
bacterial infections and mycoses
biology.organism_classification
medicine.disease
enzymology [Anaplasma phagocytophilum]
Virology
Mice, Inbred C57BL
Mutagenesis, Insertional
Mutagenesis
biology.protein
bacteria
pathology
Parasitology
metabolism
Gene Deletion
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....ac2fe12143069b915795be2ff56de84f