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The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis.

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-? and TNF-?. 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.

SUBMITTER: Mueller-Ortiz SL

PROVIDER: S-EPMC4122265 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration.

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Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors.

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Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation.

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The C5a anaphylatoxin receptor (C5aR1) protects against Listeria monocytogenes infection by inhibiting type 1 IFN expression.

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The Complement Anaphylatoxins C5a and C3a Suppress IFN-β Production in Response to <i>Listeria monocytogenes</i> by Inhibition of the Cyclic Dinucleotide-Activated Cytosolic Surveillance Pathway.

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Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections.

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| S-EPMC7115502 | biostudies-literature

C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts.

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