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Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection

The complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1(−/−) mice exhibited greater susceptibility to S. aure...

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Autores principales: Horst, Sarah A., Itzek, Andreas, Klos, Andreas, Beineke, Andreas, Medina, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693161/
https://www.ncbi.nlm.nih.gov/pubmed/26512700
http://dx.doi.org/10.3390/pathogens4040722
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author Horst, Sarah A.
Itzek, Andreas
Klos, Andreas
Beineke, Andreas
Medina, Eva
author_facet Horst, Sarah A.
Itzek, Andreas
Klos, Andreas
Beineke, Andreas
Medina, Eva
author_sort Horst, Sarah A.
collection PubMed
description The complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1(−/−) mice exhibited greater susceptibility to S. aureus bloodstream infection than wild type and C5aR2(−/−) mice, as demonstrated by the significantly higher bacterial loads in the kidneys and heart at 24 h of infection, and by the higher levels of inflammatory IL-6 in serum. Histological and immunohistochemistry investigation of infected kidneys at 24 h after bacterial inoculation revealed a discrete infiltration of neutrophils in wild type mice but already well-developed abscesses consisting of bacterial clusters surrounded by a large number of neutrophils in both C5aR1(−/−) and C5aR2(−/−) mice. Furthermore, blood neutrophils from C5aR1(−/−) mice were less efficient than those from wild type or C5aR2(−/−) mice at killing S. aureus. The requirement of C5aR1 for efficient killing of S. aureus was also demonstrated in human blood after disrupting C5a-C5aR1 signaling using specific inhibitors. These results demonstrated a role for C5aR1 in S. aureus clearance as well as a role for both C5aR1 and C5aR2 in the orchestration of the inflammatory response during infection.
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spelling pubmed-46931612016-01-06 Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection Horst, Sarah A. Itzek, Andreas Klos, Andreas Beineke, Andreas Medina, Eva Pathogens Article The complement anaphylatoxin C5a contributes to host defense against Staphylococcus aureus. In this study, we investigated the functional role of the two known C5a receptors, C5aR1 and C5aR2, in the host response to S. aureus. We found that C5aR1(−/−) mice exhibited greater susceptibility to S. aureus bloodstream infection than wild type and C5aR2(−/−) mice, as demonstrated by the significantly higher bacterial loads in the kidneys and heart at 24 h of infection, and by the higher levels of inflammatory IL-6 in serum. Histological and immunohistochemistry investigation of infected kidneys at 24 h after bacterial inoculation revealed a discrete infiltration of neutrophils in wild type mice but already well-developed abscesses consisting of bacterial clusters surrounded by a large number of neutrophils in both C5aR1(−/−) and C5aR2(−/−) mice. Furthermore, blood neutrophils from C5aR1(−/−) mice were less efficient than those from wild type or C5aR2(−/−) mice at killing S. aureus. The requirement of C5aR1 for efficient killing of S. aureus was also demonstrated in human blood after disrupting C5a-C5aR1 signaling using specific inhibitors. These results demonstrated a role for C5aR1 in S. aureus clearance as well as a role for both C5aR1 and C5aR2 in the orchestration of the inflammatory response during infection. MDPI 2015-10-23 /pmc/articles/PMC4693161/ /pubmed/26512700 http://dx.doi.org/10.3390/pathogens4040722 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Horst, Sarah A.
Itzek, Andreas
Klos, Andreas
Beineke, Andreas
Medina, Eva
Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title_full Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title_fullStr Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title_full_unstemmed Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title_short Differential Contributions of the Complement Anaphylotoxin Receptors C5aR1 and C5aR2 to the Early Innate Immune Response against Staphylococcus aureus Infection
title_sort differential contributions of the complement anaphylotoxin receptors c5ar1 and c5ar2 to the early innate immune response against staphylococcus aureus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693161/
https://www.ncbi.nlm.nih.gov/pubmed/26512700
http://dx.doi.org/10.3390/pathogens4040722
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