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Oral clarithromycin enhances airway IgA immunity through induction of IgA class switching recombination and B-cell activating factor of the tumor necr

tetano

Editor, Senior Moderator
J Virol. 2012 Aug 15. [Epub ahead of print]
Oral clarithromycin enhances airway IgA immunity through induction of IgA class switching recombination and B-cell activating factor of the tumor necrosis factor family molecule on mucosal dendritic cells in mice infected with influenza A virus.
Takahashi E, Kataoka K, Indalao IL, Konoha K, Fujii K, Chida J, Mizuno D, Fujihashi K, Kido H.
Source

Division of Enzyme Chemistry, Institute for Enzyme Research.
Abstract

We previously reported that the macrolide antibiotic clarithromycin (CAM) enhanced mucosal immune response in pediatric influenza, particularly in children treated with the antiviral neuraminidase inhibitor oseltamivir (OSV) with low production of mucosal anti-viral secretory-IgA (S-IgA). The aims of the present study were to confirm the effects of CAM on S-IgA immune responses, by using influenza A virus (IAV)(H1N1)-infected mice treated with or without OSV, and determine the molecular mechanisms responsible for the induction of mucosal IgA class switch recombination in IAV-infected CAM-treated mice. The anti-IAV S-IgA responses and expression levels of IgA class switch recombination associated-molecules were examined in bronchus-lymphoid tissues and spleen of infected mice. We also assessed neutralization activities of S-IgA against IAV. Data show that CAM enhanced anti-IAV S-IgA induction in the airway of infected mice and restored the attenuated anti-viral S-IgA levels in OSV-treated mice to the levels in the vehicle treated mice. The expression levels of B-cell activating factor of the tumor necrosis factor family (BAFF) molecule on mucosal dendritic cells as well as those of activation-induced cytidine deaminase and Iμ-Cα transcripts on B cells were enhanced by CAM, compared with the levels without CAM-treatment, but had no effect on the expression BAFF receptor on B cells. Enhanced neutralization activities by CAM of airway S-IgA against IAV in vitro and re-infected mice were observed. This study identifies that CAM enhances S-IgA production and neutralizing activities through the induction of IgA class switch recombination and upregulation of BAFF molecules in mucosal dendritic cells in IAV-infected mice.

PMID:
22896605
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22896605
 
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