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The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Aug 01; Vol. 193 (3), pp. 1278-89. Date of Electronic Publication: 2014 Jun 30. - Publication Year :
- 2014
-
Abstract
- Listeria monocytogenes is a Gram-positive intracellular bacterium that is acquired through tainted food and may lead to systemic infection and possible death. Despite the importance of the innate immune system in fighting L. monocytogenes infection, little is known about the role of complement and its activation products, including the potent C3a anaphylatoxin. In a model of systemic L. monocytogenes infection, we show that mice lacking the receptor for C3a (C3aR(-/-)) are significantly more sensitive to infection compared with wild-type mice, as demonstrated by decreased survival, increased bacterial burden, and increased damage to their livers and spleens. The inability of the C3aR(-/-) mice to clear the bacterial infection was not caused by defective macrophages or by a reduction in cytokines/chemokines known to be critical in the host response to L. monocytogenes, including IFN-γ and TNF-α. Instead, TUNEL staining, together with Fas, active caspase-3, and Bcl-2 expression data, indicates that the increased susceptibility of C3aR(-/-) mice to L. monocytogenes infection was largely caused by increased L. monocytogenes-induced apoptosis of myeloid and lymphoid cells in the spleen that are required for ultimate clearance of L. monocytogenes, including neutrophils, macrophages, dendritic cells, and T cells. These findings reveal an unexpected function of C3a/C3aR signaling during the host immune response that suppresses Fas expression and caspase-3 activity while increasing Bcl-2 expression, thereby providing protection to both myeloid and lymphoid cells against L. monocytogenes-induced apoptosis.<br /> (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Apoptosis genetics
Apoptosis Regulatory Proteins deficiency
Apoptosis Regulatory Proteins genetics
Caspase 3 metabolism
Caspase Inhibitors pharmacology
Complement C3a immunology
Disease Models, Animal
Down-Regulation genetics
Down-Regulation immunology
Immunosuppressive Agents pharmacology
Immunosuppressive Agents therapeutic use
Listeria monocytogenes pathogenicity
Listeriosis genetics
Lymphocytes immunology
Lymphocytes metabolism
Lymphocytes pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells immunology
Myeloid Cells metabolism
Myeloid Cells pathology
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Receptors, Complement deficiency
Receptors, Complement genetics
Signal Transduction genetics
Signal Transduction immunology
Up-Regulation genetics
Up-Regulation immunology
fas Receptor antagonists & inhibitors
fas Receptor biosynthesis
Apoptosis immunology
Apoptosis Regulatory Proteins physiology
Complement C3a metabolism
Listeria monocytogenes immunology
Listeriosis immunology
Listeriosis pathology
Receptors, Complement physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 193
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24981453
- Full Text :
- https://doi.org/10.4049/jimmunol.1302787