Abstract |
During relapsing fever borreliosis, a high pathogen load in the blood occurs at times of peak bacteremia. Specific IgM Abs are responsible for spirochetal clearance so in absence of B cells there is persistent high-level bacteremia. Previously, we showed that B cell-deficient mice persistently infected with Borrelia turicatae produce high levels of IL-10 and that exogenous IL-10 reduces bacteremia. This suggested that IL-10 helps reduce bacteremia at times of high pathogen load by a B cell-independent mechanism, most likely involving innate immunity. To investigate this possibility, we compared B. turicatae infection in RAG2/IL-10(-/-) and RAG2(-/-) mice. The results showed that IL-10 deficiency resulted in significantly higher bacteremia, higher TNF levels, and early mortality. Examination of the spleen and peripheral blood showed markedly increased apoptosis of immune cells in infected RAG2/IL-10(-/-) mice. Neutralization of TNF reduced apoptosis of leukocytes and splenocytes, increased production of IFN-gamma by NK cells, increased phagocytosis in the spleen, decreased spirochetemia, and rescued mice from early death. Our results indicate that at times of high pathogen load, as during peak bacteremia in relapsing fever borreliosis, IL-10 protects innate immune cells from apoptosis via inhibition of TNF resulting in improved pathogen control.
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Authors | Diana Londoño, Adriana Marques, Ronald L Hornung, Diego Cadavid |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 181
Issue 3
Pg. 2076-83
(Aug 01 2008)
ISSN: 1550-6606 [Electronic] United States |
PMID | 18641346
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- DNA-Binding Proteins
- Rag2 protein, mouse
- Tumor Necrosis Factor-alpha
- Interleukin-10
- Interferon-gamma
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Topics |
- Animals
- Antibodies
(immunology, pharmacology)
- Apoptosis
- Bacteremia
(genetics, immunology, metabolism, pathology)
- Borrelia
(immunology, pathogenicity)
- Borrelia Infections
(genetics, immunology, metabolism, pathology)
- DNA-Binding Proteins
(deficiency, genetics, metabolism)
- Female
- Interferon-gamma
(biosynthesis)
- Interleukin-10
(deficiency, genetics, immunology, metabolism)
- Killer Cells, Natural
(immunology, metabolism)
- Mice
- Mice, Knockout
- Spleen
(immunology, metabolism)
- Survival Rate
- Tumor Necrosis Factor-alpha
(biosynthesis, immunology)
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