Description of Research Expertise:
Immunology of Chronic Leishmania Infection
IgG and FcgammaR interactions
Key words: immunology, immunoparasitology, Leishmania, parasite, IL-10, Fcgamma R, cysteine proteinase
Worldwide there are 12 million people infected with the single-celled parasite Leishmania, with 2 million new infections a year. Spread by sandfly bites, this parasite causes fatal disease of the internal organs as well as non-healing and potentially disfiguring diseases of the skin and mucous membranes. Thirteen Gulf War veterans contracted an unusual version of leishmaniasis that affected the internal organs, even though this strain exclusively causes skin disease in local populations. Over 1200 cases of cutaneous leishmaniasis have occurred in the US troops stationed in Iraq and Afghanistan.
We have been studying infection of mice by Leishmania mexicana, attempting to understand why this parasite causes non-healing disease, whereas a related parasite, L. major, causes lesions that heal. We have found that the cytokine IL-10 suppresses a protective T cell-mediated IFN-gamma response and that IL-10 is therefore required for chronic infection. IL-10 production is triggered by antibodies on the surface of parasites. FcgammaR, likely on macrophages, are also required for chronic disease to occur. We are trying to determine the IgG isotypes and FcγR types involved in this IL-10 process as well as the cellular source of IL-10 (macrophages, T cells, B cells, other?) in order to better understand the mechanism of this suppressive response and to help guide vaccine development. More recently we began new investigations into the role of glycolipids as parasite surface targets of IgG.
A better understanding of the immune mechanisms of Leishmania infection may give insights into many other diseases that involve cell-mediated immunity, especially those caused by pathogens that live inside host cells such as tuberculosis, toxoplasmosis, and HIV.
Buxbaum, L.U.: Interleukin-10 from T cells but not macrophages and granulocytes, is required for chronic disease in Leishmania Mexicana infection Infection and Immunity 83 : 1366-1371,2015.
Brennick, M.J., Delikatny, J., Pack, A.I., Pickup, S., Shinde, S., Zhu, J-X, Roscoe, I., Kim, D.Y., Buxbaum, L.U., Cater, J.R., and Schwab, R.J.: Tongue Fat Infiltration in Obese vs. Lean Zucker Rats Sleep 37 : 1095-1102,2014.
Buxbaum LU: IL-10 from T cells, but not macrophages is required for chronic disease in Leishmania mexicana infection American Association of Immunologists, Immunology 2013, Honolulu, HI : 2013.
Buxbaum LU: Leishmania mexicana Infection Induces IgG to Parasite Surface Glycoinositol Phospholipids That Can Induce IL-10 in Mice and Humans PLoS Neglected Tropical Diseases 7 : e2224,2013.
Jackson-Malik, P., McLaughlin, M., O’Hara, K.T., and Buxbaum, L.: Rapid Oral Fluid Testing for HIC in Veterans with Mental Health Diagnoses and Residing in Community Assisted Living Facilities. Practice Based on Evidence: The Future of Nursing University of Maryland, School of Nursing and VA Maryland Health Care System, Baltimore, MD : 2012.
Buxbaum LU: IL-10 From Macrophages and Granulocytes Is Not Required For Chronic Disease In Leishmania mexicana Infection Woods Hole Immunoparasitology Meeting, Woods Hole, MA : 2011.
Buxbaum LU*, DeRitis P, Chu N, and Conti PA.* corresponding author: Eliminating mouse norovirus by cross-fostering Journal of the American Association for Laboratory Animal Science 4 (495-9): 2011.
Jackson-Malik, McLaughlin M, O’Hara KT, and Buxbaum LU: Identifying and measuring the prevalence of HIV 2010 State of the Science Congress on Nursing Research, Washington, DC : 2010.
Jackson-Malik, P., McLaughlin, M., O’Hara, K.T., and Buxbaum, LU: Identifying and Measuring the Prevalence of Veterans with Chronic Bloodborne Illness: Testing for HIV in Community Care Residents Academy Health’s Health Services Research 2010 Annual Research Meeting, Boston, MA : 2010.
Buxbaum LU: Leishmania mexicana Infection Induces Antibody Responses to Parasite Surface Glycolipids that Can Induce IL-10 and Suppress IL-12 from Macrophages American Association of Immunologists, Baltimore, MD : 2010.