Influenza A virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection.
Mucosal Immunol
; 10(2): 460-469, 2017 03.
Article
in En
| MEDLINE
| ID: mdl-27220813
ABSTRACT
During influenza A virus (IAV) infection, changes in the lung's physical and immunological defenses predispose the host to bacterial superinfections. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that have beneficial or harmful functions during infection. We investigated the iNKT cells' role in a model of invasive pneumococcal superinfection. The use of Jα18-/- mice indicated that iNKT cells limited susceptibility to influenza-pneumococcal infection and reduced the lethal synergism. This role did not depend on immune-based anti-bacterial mechanisms. At the time of bacterial exposure, iNKT cells from IAV-experienced mice failed to produce antipneumococcal interferon-γ and adoptive transfer of fresh iNKT cells before Streptococcus pneumoniae challenge did not restore anti-bacterial host defenses. Impaired iNKT cell activation in superinfected animals was related to the IAV-induced immunosuppressive cytokine interleukin-10 (IL-10), rather than to an intrinsic functional defect. IL-10 dampened the activation of iNKT cells in response to pneumococci by inhibiting the production of IL-12 by pulmonary monocyte-derived dendritic cells. Neutralization of IL-10 restored iNKT cell activation and tends to increase resistance to secondary bacterial infection. Overall, iNKT cells have a beneficial role (upstream of bacterial colonization) in controlling influenza-pneumococcal superinfection, although they represent novel targets of immunosuppression at the time of bacterial challenge.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Influenza A virus
/
Pneumococcal Infections
/
Streptococcus pneumoniae
/
Interleukin-10
/
Orthomyxoviridae Infections
/
Natural Killer T-Cells
/
Lung
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mucosal Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Document type:
Article
Affiliation country: