A possible mechanism linking cigarette smoke to higher incidence of respiratory infection and asthma.
T helper type 1 (Th1) cells are responsible for cell-mediated immunity against invading pathogens, while Th2 cells provide help to B cells and control allergic responses. The polarization of naïve Th cells into Th1 or Th2 subsets is controlled by dendritic cells (DCs) migrating from the periphery to draining lymph nodes. Migrating DCs carry not only antigen-specific 'signal 1' and costimulatory 'signal 2', but also Th-polarizing 'signal 3' that reflects the nature of the pathogen and the character of the infected tissue. Any changes imposed by external factors on the DC lifecycle may result in an inappropriate immune response. Here we show that DCs developed in a nicotinic environment (nicDCs) fail to support the terminal development of effector memory Th1 cells due to their differential expression of costimulatory molecules and lack of IL-12 production. Interestingly, they adopt critical Th1-promoting function necessary to prevent and fight infections only when the total balance of environmental signals strongly favors Th1 immunity. Notably, in a Th2-biased environment, nicDCs provoke stronger than normal Th2 responses which predisposes the development and exacerbation of asthma. These results help explain the two opposing effects of cigarette smoke on respiratory immune defense mechanisms: (a) immunosuppression against infectious agents and (b) exacerbation of asthma.
Nouri-Shirazi
Mahyar
M
Department of Biomedical Sciences, Immunology Laboratory, Texas A&M University System Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA. MNShirazi@bcd.tamhsc.edu
Guinet
Elisabeth
E
D001249:Asthma / Q000209:etiology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology; D012141:Respiratory Tract Infections; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
D007371:Interferon-gamma; D015232:Dinoprostone