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The C5a Anaphylatoxin Receptor (C5aR1) Protects against Listeria monocytogenes Infection by Inhibiting Type 1 IFN Expression
- Source :
- The Journal of Immunology. 193:5099-5107
- Publication Year :
- 2014
- Publisher :
- The American Association of Immunologists, 2014.
-
Abstract
- Listeria monocytogenes is a major cause of mortality resulting from food poisoning in the United States. In mice, C5 has been genetically linked to host resistance to listeriosis. Despite this genetic association, it remains poorly understood how C5 and its activation products, C5a and C5b, confer host protection to this Gram-positive intracellular bacterium. In this article, we show in a systemic infection model that the major receptor for C5a, C5aR1, is required for a normal robust host immune response against L. monocytogenes. In comparison with wild-type mice, C5aR1−/− mice had reduced survival and increased bacterial burden in their livers and spleens. Infected C5aR1−/− mice exhibited a dramatic reduction in all major subsets of splenocytes, which was associated with elevated caspase-3 activity and increased TUNEL staining. Because type 1 IFN has been reported to impede the host response to L. monocytogenes through the promotion of splenocyte death, we examined the effect of C5aR1 on type 1 IFN expression in vivo. Indeed, serum levels of IFN-α and IFN-β were significantly elevated in L. monocytogenes–infected C5aR1−/− mice. Similarly, the expression of TRAIL, a type 1 IFN target gene and a proapoptotic factor, was elevated in NK cells isolated from infected C5aR1−/− mice. Treatment of C5aR1−/− mice with a type 1 IFNR blocking Ab resulted in near-complete rescue of L. monocytogenes–induced mortality. Thus, these findings reveal a critical role for C5aR1 in host defense against L. monocytogenes through the suppression of type 1 IFN expression.
- Subjects :
- Male
Anaphylatoxins
Immunology
Complement C5b
Gene Expression
Apoptosis
Complement C5a
Spleen
medicine.disease_cause
Article
Antibodies
TNF-Related Apoptosis-Inducing Ligand
Mice
Immune system
Listeria monocytogenes
In vivo
medicine
Splenocyte
Animals
Immunology and Allergy
Listeriosis
Anaphylatoxin
Lymphocytes
Receptor
Receptor, Anaphylatoxin C5a
Receptors, Interferon
Mice, Knockout
biology
Caspase 3
Interferon-alpha
Interferon-beta
Survival Analysis
Bacterial Load
medicine.anatomical_structure
Liver
biology.protein
Antibody
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 193
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....abbb150c9857aedd951d05ee7ddd1804