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Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease.
- Source :
-
PLoS pathogens [PLoS Pathog] 2011 Oct; Vol. 7 (10), pp. e1002244. Date of Electronic Publication: 2011 Oct 06. - Publication Year :
- 2011
-
Abstract
- A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12-15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses.
- Subjects :
- Animals
Asthma microbiology
Asthma pathology
Disease Models, Animal
Eosinophils immunology
Female
Haemophilus Infections microbiology
Haemophilus Infections pathology
Immunity, Cellular
Inflammation pathology
Interferon-gamma immunology
Interleukin-13 immunology
Interleukin-17 metabolism
Interleukin-5 immunology
Mice
Mice, Inbred BALB C
Ovalbumin adverse effects
Ovalbumin immunology
Phenotype
T-Lymphocytes, Regulatory immunology
Th17 Cells cytology
Th17 Cells immunology
Asthma immunology
Haemophilus Infections immunology
Haemophilus influenzae pathogenicity
Interleukin-17 immunology
Neutrophils immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 7
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 21998577
- Full Text :
- https://doi.org/10.1371/journal.ppat.1002244