Peter Mancuso, Ph.D.
Department of Environmental Health Sciences
Regulation of the innate immune response against bacterial pneumonia, Role of the eicosanoids and their receptors in pneumococcal pneumonia, Impact of second hand tobacco smoke in lung disease, Role of adiponectin and leptin in inflammation and infection in obesity
Current Research Activity
In my laboratory, we are currently working on projects that examine; 1) The ability of leptin and adiponectin to regulate the immune response to infection and; 2) The consequence of second hand cigarette smoke exposure and the pulmonary innate immune response against pneumococcal pneumonia.
Energy malnutrition and being underweight are major risk factors associated with an increased risk of infections of the lower respiratory tract. In particular, Streptococcus pneumoniae is the most commonly isolated organism from patients with community-acquired pneumonia and a leading cause of death in children under the age of 5 years and the elderly. We have examined the role of leptin, a hormone produced by adipose tissue that is reduced in the energy malnourished and is known to regulate innate immune responses, during bacterial pneumonia. We have reported that leptin-deficiency impairs host defense against bacterial pneumonia and have identified critical intracellular signaling pathways by which the leptin receptor regulates the innate immune response in alveolar macrophages. Currently, we are examining the role that leptin plays in the adaptive immune response to infection and humoral immunity. In contrast, adiponectin is an anti-inflammatory hormone produced by adipose tissue that increases in calorie restriction and aging and declines with increasing fat mass and inflammation. We currently are examining the mechanisms by which adiponectin down regulates pro-inflammatory mediator production in macrophages and how it impacts the innate immune response to infection.
Despite recent legislation in several states and cities to ban smoking in public places, approximately 50% of adults and 40% of children are regularly exposed to second-hand cigarette smoke in the US. Tobacco smoke exposure is the most important risk factor for invasive pneumococcal disease and an increased risk of pulmonary infections. Prostaglandin E2 (PGE2) production is increased in the lungs of smokers and is known to play an immunosuppressive role in the host response to bacterial infections. We are currently exploring the role of the EP2, a PGE2 receptor, in cigarette smoke induced immune suppression.
D.M. Aronoff, I.L. Bergin, C. Lewis, D. Goel, E. O’Brien, C.H. Serezani, M. Peters-Golden, and P. Mancuso. 2012. Prostaglandin E2 Signaling via the E Prostanoid 2 Receptor Suppresses Pulmonary Innate Immune Defense against Streptococcus pneumoniae. Prost. and other lipid mediat. 98:22-30.
P. Mancuso, M.G. Myers Jr., D. Goel, C.H.C. Serenzani, E. O’Brien, D.M. Aronoff, and M. Peters-Golden. 2012. Ablation of leptin receptor mediated extracellular regulated kinase activation impairs host defense against bacterial pneumonia. J Immunol 189: 867-75.
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.