Joseph P. Mizgerd, Sc.D.
Professor of Medicine and Microbiology
Director, Pulmonary Center
72 East Concord Street
Office: R-3; 617-638-5201
Lab: R224; 617-638-5272
B.A. Amherst College
Sc.D. Harvard School of Public Health
Acute lower respiratory tract infections cause a terrible public health burden at present, with potential for worse in the coming years. The outcome of these infections is determined by innate immune responses (such as neutrophil recruitment and activation), necessary for host defense but also contributing to lung injury. Innate immune responses in the lungs require the coordinated expression of diverse mediators including adhesion molecules, chemokines, colony stimulating factors, and cytokines that are absent or present only at low levels in uninfected lungs, but are expressed at high levels during infection. Similar mediators are induced during most lung infections, although individual mediators can have different roles during different infections. The coordinated expression suggests programs of gene regulation. NF-kappaB transcription factors are critical to the gene expression program directing innate immunity in the lungs, with RelA inducing innate immunity genes mediating host defense and p50 counteracting this gene induction to prevent lung injury. Other transcription factors are also important, such as STAT3 which both facilitates host defense and limits lung injury. These transcription factors have cell-specific roles during infection. Finally, expression of innate immunity mediators is regulated post-transcriptionally as well. An improved knowledge of the molecular mechanisms directing innate immunity in the lungs will provide new directions for preventing and curing acute lower respiratory tract infections.
- Quinton, LJ, MR Jones, BE Robson, BT Simms, JA Whitsett, JP Mizgerd. 2008. Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia. Am J Respir Cell Mol Biol 38:699-706.
- Mizgerd, JP. 2008. Mechanisms of disease: Acute lower respiratory infection. N Engl J Med 358:716-727.
- 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.
- Jones, MR, LJ Quinton, BT Simms, MM Lupa, MS Kogan, JP Mizgerd. 2006. Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia. J Infect Dis 193:360-369.
- Mizgerd, JP. 2006. Lung infection – a public health priority. PLoS Medicine 3(2):e76.
- Jones, MR, BT Simms, MM Lupa, MS Kogan, JP Mizgerd. 2005. Lung NF-kappaB activation and neutrophil recruitment require IL-1 and TNF receptor signaling during pneumococcal pneumonia. J Immunol 175:7530-7535.