Innate immune processes are sufficient for driving cigarette smoke-induced inflammation in mice

Am J Respir Cell Mol Biol. 2010 Apr;42(4):394-403. doi: 10.1165/rcmb.2008-0301OC. Epub 2009 Jun 5.


The objective of this study was to characterize the impact of cigarette smoke exposure on lung immune and inflammatory processes. BALB/c and C57BL/6 mice were exposed to cigarette smoke for 4 days (acute) or at least 5 weeks (prolonged). Both mouse strains manifested an inflammatory response after acute smoke exposure, characterized by an influx of neutrophils and mononuclear cells. Multiplex analysis revealed a greater than twofold increase of the cytokines IL-1alpha, -5, -6, and -18, as well as the chemokines monocyte chemotactic protein-1 and -3, macrophage inflammatory protein-1alpha, -beta, and -gamma, -2, -3beta, macrophage defined chemokine, granulocyte chemotactic protein-2, and interferon-gamma-inducible protein-10. In BALB/c mice, neutrophilia persisted after prolonged exposure, whereas C57BL/6 showed evidence of attenuated neutrophilia both in the bronchoalveolar lavage and the lungs. In both mouse strains, cigarette smoke exposure was associated with an expansion of mature (CD11c(hi)/major histocompatibility complex class II(hi)) myeloid dendritic cells; we observed no changes in plasmacytoid dendritic cells. Lymphocytes in the lungs displayed an activated phenotype that persisted for CD4 T cells only after prolonged exposure. In BALB/c mice, T cells acquired T helper (Th) 1 and Th2 effector function after 5 weeks of smoke exposure, whereas, in C57BL/6 mice, neither Th1 nor Th2 cells were detected. In both mouse strains, cigarette smoke exposure led to an accumulation of FoxP3+ T regulatory cells in the lungs. Studies in RAG1 knockout mice suggest that these regulatory cells may participate in controlling smoke-induced inflammation. Acute and prolonged cigarette smoke exposure was associated with inflammation, activation of the adaptive immune system, and expansion of T regulatory cells in the lungs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology
  • Animals
  • Bronchoalveolar Lavage
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Neutrophil Infiltration / genetics
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Pneumonia / etiology
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Smoking / adverse effects*
  • Smoking / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology
  • Time Factors


  • CD11c Antigen
  • Cytokines
  • Homeodomain Proteins
  • RAG-1 protein