Innate Immunity

Basic Science Research Basic Science Research

Innate Immunity of the Lung

Mission Statement

Innate immunity helps to protect the lung against infection and is a critical component of diverse lung diseases.  Our mission is to elucidate the mechanisms and functional significance of innate immune processes, with the goals of identifying factors that increase risks for lung diseases and designing new strategies for their treatment.

Background

The Innate Immunity group at the Pulmonary Center focuses on local and systemic innate immune responses to infectious, environmental, and other challenges to the lung.  Diseases of particular interest include acute respiratory infections (pneumonia), acute lung injury (ALI/ARDS), chronic obstructive pulmonary disease (COPD/emphysema), and pulmonary alveolar proteinosis.  Further advances against these diseases are predicated upon breakthroughs in the understanding of innate immunity..

We study the contributions of innate immunity to lung disease using diverse approaches including genetic engineering, molecular and cell biology, and integrative physiology.  One major focus of our work is the alveolar macrophage, particularly its development, fate, and functional roles as a resident innate immune cell.  Another emphasis is the recruitment and activation of neutrophils as additional innate immunity effector cells enlisted when resident defenses in the lung are insufficient.  Research is also illuminating the roles of structural, non-hematopoietic cells (such as alveolar epithelial cells, adipocytes and hepatocytes) in mediating local as well as systemic innate immune functions (such as the bone marrow production and release of leukocytes and the liver acute phase response).  A consistent theme to this research is the molecular mechanisms mediating the expression of gene programs that drive innate immunity, such as the transcription factors coordinating the expression of cytokines, chemokines,  colony stimulating factors, adhesion molecules, antimicrobial factors, and cytoprotective proteins.  While initiating innate immune responses is essential to fighting infections, controlling these responses is equally important and essential to limiting lung injury, mediated for example by microRNAs and repressor proteins.  Inflammatory injury results from exuberant innate immune activity in the lung, and the cellular and molecular mechanisms of repair and regeneration subsequent to lung injury represents an emerging research interest of the group.

On-going research projects:

  • Alveolar macrophage kinetics and function.
  • Neutrophil recruitment and activation in the lungs.
  • Rheostat fine-tuning of innate immune responses (transcriptional and post-transcriptional mechanisms) to fight infection without excessive lung injury.
  • The regulation and functional significance of hepatic acute phase responses during lung disease.
  • Influence of adipokines and other adipose-derived signals on lung innate immunity.
  • Repair of the injured lung, including roles of stem cells, cellular differentiation, proliferation, apoptosis, autophagy, and senescence.
  • Lentiviral vectors for elucidating and manipulating innate immunity in the lungs.

Principal Investigators:

Additional links related to Pulmonary Center Innate Immunity:

Kotton Lab

Pneumonia Biology

Immunology and Asthma

Selected Publications:

  1. Quinton LJ, Jones MR, Robson BE, Mizgerd JP. Mechanisms of the hepatic acute-phase response during bacterial pneumonia. Infect Immun 2009 77:2417-26.
  2. Wilson AA, Kwok LW, Hovav AH, Ohle SJ, Little FF, Fine A, Kotton DN. Sustained expression of alpha1-antitrypsin after transplantation of manipulated hematopoietic stem cells. Am J Respir Cell Mol Biol 2008 39:133-41.
  3. Mizgerd JP. 2008. Mechanisms of disease: Acute lower respiratory infection. N Engl J Med 358:716-727.
  4. Summer R, Little FF, Ouchi N, Takemura Y, Aprahamian T, Dwyer D, Fitzsimmons K, Suki B, Parameswaran H, Fine A, Walsh K. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. Am J Physiol Lung Cell Mol Physiol 2008 294:L1035-42.
  5. Murphy J, Summer R, Wilson AA, Kotton DN, Fine A. The prolonged life-span of alveolar macrophages. Am J Respir Cell Mol Biol 2008 38:380-5.
  6. Quinton LJ, MR Jones, BT Simms, MS Kogan, BE Robson, SJ Skerrett, JP Mizgerd. 2007. Functions and regulation of NF-kappaB RelA during pneumococcal pneumonia. J Immunol 178:1896-1903.
  7. Jones MR, Quinton LJ, Simms BT, Lupa MM, Kogan MS, Mizgerd JP. Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia. J Infect Dis 2006 193:360-9.
  8. Ieong MH, Reardon CC, Levitz SM, Kornfeld H. Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity. Am J Respir Crit Care Med 2000 162:966-70.
Primary teaching affiliate
of BU School of Medicine