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C5a receptor1 inhibition alleviates influenza virus-induced acute lung injury
- Source :
- International Immunopharmacology. 59:12-20
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection. The results showed that blocking the C5a-C5aR1 axis alleviated ALI by inhibiting endothelial cell activation and dampening the host immune response (i.e., reduced TNF-α, IL-1β, IL-6, IP-10, MCP-1, IL-12p70, and IFN-γ concentrations in plasma), particularly CTL-mediated immunopathology. Furthermore, blockade of the C5a-C5aR1 axis inhibited viral replication in lung tissue. Taken together, the results indicate that the C5a-C5aR1 axis plays an important role in the outcome of ALI induced by influenza virus infection and that regulation of complement activation, particularly the C5aR1 inhibition, is a promising intervention and adjunctive treatment.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Acute Lung Injury
Immunology
Complement C5a
Lung injury
Virus Replication
medicine.disease_cause
Virus
03 medical and health sciences
Immune system
Orthomyxoviridae Infections
Immunopathology
Influenza A virus
medicine
Animals
Immunology and Allergy
Complement Activation
Lung
Receptor, Anaphylatoxin C5a
Peroxidase
Mice, Knockout
Pharmacology
Mice, Inbred BALB C
Innate immune system
business.industry
Antibodies, Monoclonal
Immunotherapy
respiratory system
Intercellular Adhesion Molecule-1
030104 developmental biology
Adjunctive treatment
Cytokines
Female
business
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....96e9a9e614bbb22c72d38456774e178e