Deletion of the complement C5a receptor alleviates the severity of acute pneumococcal otitis media following influenza A virus infection in mice

Autor: Garrett M. Lambert, Caitlin Clancy, Andrew S. Bowman, Joshua M. Thurman, Yong Xing Li, H. H. Tong, Kelsey Douthitt, Yujuan He, Gregory L. Stahl
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Viral Diseases
Gene Expression
lcsh:Medicine
Complement C5a
Pathogenesis
Pathology and Laboratory Medicine
medicine.disease_cause
Severity of Illness Index
Mice
Influenza A Virus
H1N1 Subtype
Medicine and Health Sciences
Influenza A virus
lcsh:Science
Complement Activation
Avian influenza A viruses
Mice
Knockout
Multidisciplinary
Coinfection
Animal Models
Medical microbiology
3. Good health
Pneumococcal infections
Streptococcus pneumoniae
Infectious Diseases
Superinfection
Acute Disease
Host-Pathogen Interactions
Complement C3a
Female
medicine.symptom
Complement Factor B
Research Article
Immunology
Mouse Models
Biology
Research and Analysis Methods
Microbiology
Complement factor B
Pneumococcal Infections
Model Organisms
Orthomyxoviridae Infections
medicine
Animals
Influenza viruses
Anaphylatoxin
Receptor
Anaphylatoxin C5a
Biology and life sciences
Complement C1q
Eustachian Tube
lcsh:R
Viral pathogens
medicine.disease
Immunity
Innate
Influenza
Microbial pathogens
Complement system
Mice
Inbred C57BL
Otitis Media
Otitis
Viral Pneumonia
Otorhinolaryngology
lcsh:Q
Gene Deletion
Orthomyxoviruses
Zdroj: PLoS ONE, Vol 9, Iss 4, p e95160 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: There is considerable evidence that influenza A virus (IAV) promotes adherence, colonization, and superinfection by S. pneumoniae (Spn) and contributes to the pathogenesis of otitis media (OM). The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa−/−) or factor B (Bf −/−) exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR) demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.
Databáze: OpenAIRE
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