title: Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses in the lung during influenza virus infection.
abstract: BACKGROUND
  It is incompletely understood how cigarette smoke (CS) exposure affects lung mucosal immune responses during viral respiratory infections. B cell activating factor belonging to the tumor necrosis factor family (BAFF) plays an important role in the induction of secretory immunoglobulin A (S-IgA) which is the main effector of the mucosal immune system. We therefore investigated the effects of CS exposure on BAFF expression and S-IgA responses in the lung during influenza virus infection.
  
  
  METHODS
  Mice were exposed to CS and/or infected with influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed for BAFF expression, influenza-specific S-IgA level and histological changes. Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda) expression was determined. BEAS-2B cells were treated with CS extract (CSE), influenza virus, interferon beta or N-acetylcysteine and BAFF expression was measured.
  
  
  RESULTS
  CS inhibited BAFF expression in the lung, particularly after long-term exposure. BAFF and S-IgA levels were increased during influenza virus infection. Three-month CS exposure prior to influenza virus infection resulted in reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary inflammation on day 7 after infection. Prior CS exposure also caused decreased Aicda expression in lung B cells during infection. Neutralization of BAFF in the lung resulted in reduced S-IgA levels during influenza virus infection. CSE inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B cells, while this inhibition of BAFF by CSE was prevented by pretreatment with the antioxidant N-acetylcysteine.
  
  
  CONCLUSIONS
  Our findings indicate that CS may hinder early mucosal IgA responses in the lung during influenza virus infection through oxidative inhibition of BAFF, which might contribute to the increased incidence and severity of viral infections in smokers.
authors: Jianmiao
authors: J
authors: Wang
authors: Qinghai
authors: Q
authors: Li
authors: Jungang
authors: J
authors: Xie
authors: Yongjian
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000378:metabolism*; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D008297:Male; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D012307:Risk Factors; D012906:Smoke / Q000009:adverse effects; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D053264:B-Cell Activating Factor; D007071:Immunoglobulin A, Secretory; D012906:Smoke; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D014028:Tobacco Smoke Pollution