Peter Mancuso, Ph.D.
Associate Professor, Department of Environmental Health Sciences
http://research.sph.umich.edu/index.php?g=11&s=home

pmancuso@umich.edu

Research description

Adipokine regulation of macrophage effector functions in bacterial pneumonia, Role of E-prostanoid receptors in pneumococcal pneumonia. Tobacco smoke induced immune suppression.

Current Research Activity

In my laboratory, we are currently working on two projects; 1) The regulation of pulmonary host defense by leptin and 2) Tobacco smoke exposure and pulmonary innate immune responses against pneumococcal pneumonia.

Leptin is a hormone produced by adipose tissue that is reduced in the energy malnourished and is known to regulate innate immune responses. During bacterial pneumonia, leptin levels increase in the lung and leptin-deficient mice are more susceptible to bacterial pneumonia. We've also found that the exogenous administration of leptin in vivo to leptin-deficient animals reconstitutes antibacterial host defense endpoints in vivo and in vitro. Currently, we are determining the target cells in the lung for leptin's action and the molecular mechanisms by which it regulates pulmonary host defense by examining the importance of distinct leptin receptor signaling pathways in alveolar macrophages and neutrophil during phagocytosis and killing of S. pneumoniae in vitro. These studies will define leptin responses in the context of bacterial pneumonia and provide novel insights into the mechanisms by which leptin regulates innate immune responses against bacterial pathogens.

Tobacco smoke exposure is associated with an increased risk of pulmonary infections. While smoking cessation does improve general respiratory health, the risk of infection in former smokers remains for several years. We are currently exploring the mechanisms by which tobacco smoke exposure suppresses alveolar macrophage proinflammatory mediator synthesis and effector functions using a murine model of pneumococcal pneumonia.

Representative Publications

P. Mancuso, M. Peters-Golden, D. Goel, J. Goldberg, T.G. Brock, and M.G. Myers, Jr. 2011. Deletion of Leptin Receptor Mediated STAT3 Signaling Enhances Pulmonary Host Defense against Pneumococcal Pneumonia.  J Immunol.  186:1081-90.

J. C. Phipps, D. Aronoff, J.L. Curtis, D. Goel, and P. Mancuso. 2010. Cigarette smoke exposure impairs pulmonary host defense against pneumococcal pneumonia. Infect Immun. 78:1214-1220.

P. Mancuso, C. Lewis, C.H. Serezani, D. Goel, and M. Peters-Golden. 2010. Intrapulmonary Administration of Leukotriene B4 Enhances Pulmonary Host Defense against Pneumococcal Pneumonia. Infect Immun. 78:2264-2271.

D.M. Aronoff, C. Lewis, C. H. Serezani, K. A. Eaton, J. C. Phipps, M.          Peters-Golden, and P. Mancuso. 2009. E prostanoid 3 receptor deletion protects mice from lethal Streptococcus pneumoniae infection. J Immunol.183: 2642-2649.

Hsu, A, D. M. Aronoff, J. Phipps, D. Goel, and P. Mancuso. 2007. Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Clin Exp Immunol. 150:332-339.

Mancuso, P., G. Huffnagle, M. Olszewski, J. Phipps, and M. Peters-Golden. 2006. Leptin corrects host defense defects following acute starvation in murine pneumococcal pneumonia. Am J RespirCrit Care Med 173:212-218.

Mancuso, P ., C.A. Canetti , Gottschalk, A, P. K. Tithof, and M. Peters-Golden. 2004. Leptin enhances macrophage leukotriene synthesis by augmenting arachidonic acid release and cPLA 2 g protein expression. Am J Physiol Lung Cell Mol Physiol. 287: L497 - L502 .

S. I. Moore, G.B. Huffnagle, G.H. Chen, E. White, P. Mancuso . 2003. Leptin modulates neutrophil phagocytosis of K. pneumoniae. Infect. Immune. 71:4182-4185.

Mancuso, P., A. Gottschalk, S.Phare, M. Peters-Golden, N. Lukacs, and G. Huffnagle. 2002. Leptin-deficient mice exhibit impaired host defense in gram-negative pneumoni a. J Immuno l. 168:4018-4024.