Thomas B. Nutman, M.D.
Senior Investigator
Chief, Helminth Immunology Section
Helminth Immunology Section
Description of Research Program
The major interests of the Helminth Immunology Section relate to the host immune responses to parasitic helminth infection (primarily filariasis, loiasis, and onchocerciasis) with particular emphasis on the following:
- Regulation of these responses and their genetic control
- Regulation of human IgG4 and IgE production
- Mechanisms of eosinophil activation and eosinophilia
- The clinical expression, diagnosis, treatment and control of human helminth infections
- Clinical expression, diagnosis, treatment, and control of human helminth infections
- Influence of helminth infections on other non-parasitic infectious diseases and atopy
The focus of the section is the study of host resistance and immune regulation in parasitic helminth infections of global importance. The ultimate goal of this work is prevention of infection and disease. Our research on the human host response to helminth infection has provided insights into both the regulatory and effector mechanisms utilized by the human immune system.
Much of our work involves the analysis of host-parasite interaction using in vitro systems and studies of cells from infected patients ex vivo. Current activities include functional mapping of the earliest host-parasite interaction that influences the polarized immune responses that are the hallmarks of these infections.
Because the immune response to helminth parasites has all of the hallmarks of immediate hypersensitivity reactions—tissue and blood eosinophilia, IgE and IgG4 elevations, and the presence of tissue mast cells and basophils—understanding the regulation of each of these processes is of paramount importance. Thus, another major focus of our work involves the study of eosinophil differentiation and activation, the control of isotype switching, and basophils as an amplifier of the T-cell response to parasitic infection.
The Helminth Immunology Section, along with others in the Laboratory of Parasitic Diseases, has played a major role in the training of physicians for careers in tropical medicine. The ability to combine bench research with clinical research training has allowed many of the physicians coming to our section to pursue academic careers. The clinically based research in the Helminth Immunology Section has focused on these four major themes:
- Definition of clinical syndromes and their underlying pathogeneses
- Chemotherapy
- Prevention of post-treatment adverse reactions
- New methods for diagnosis
Research Group Members
Bottom row (left to right): Grace Maldarelli, Siddhartha Mahanty, Cathy Steel, Roshan Ramanathan, Tamisha Canady, Simon Metenou, Amy Klion, Lily Mahapatra; Middle row: Princess Ogbogu; Top row: Sasi Bennuru, Subash Babu, Tom Nutman, Joe Kubofcik, Erick Scott, Roshanak Semnani
Awards
- Bailey K. Ashford Medal from the American Society of Tropical Medicine and Hygiene
- NIAID Merit Award
- Physicians Professional Advisory Committee to the Surgeon General Physician Researcher of the Year
- U.S. Public Health Service (PHS) Achievement Medal
- PHS Commendation Medal
- PHS Outstanding Service Medal
- PHS Unit Commendation Medal
Selected Publications
To view a complete listing, visit PubMed.
Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M. Metcalfe DD, Dunbar C, Nutman TB. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2004 Jan 15;103(2):473-8.
Babu S, Blauvelt CP, Kumaraswami V, Nutman TB. Cutting edge: diminished T cell TLR expression and function modulates the immune response in human filarial infection. J Immunol. 2006 Apr 1;176(7):3885-9.
Babu S, Blauvelt CP, Kumaraswami V, Nutman TB. Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J Immunol. 2006 Mar 1;176(5): 3248-56.
Mitre E, Chien C, Nutman TB. CD4(+) (and not CD25+) T cells are the predominant interleukin-10-producing cells in the circulation of filaria-infected patients. J Infect Dis. 2008 Jan 1;197(1):94-101.
Semnani RT, Venugopal PG, Leifer CA, Mostbock S, Sabzevari H, Nutman TB. Inhibition of TLR3 and TLR4 function and expression in human dendritic cells by helminth parasites. Blood. 2008 Aug 15;112(4):1290-8.
Keiser PB, Coulibaly Y, Kubofcik J, Diallo AA, Klion AD, Traoré SF, Nutman TB. Molecular identification of Wolbachia from the filarial nematode Mansonella perstans. Mol Biochem Parasitol. 2008 Aug;160(2):123-8.
Ramanathan R, Burbelo PD, Groot S, Iadarola MJ, Neva FA, Nutman TB. A luciferase immunoprecipitation systems assay enhances the sensitivity and specificity of diagnosis in Strongyloides stercoralis infection. J Infect Dis. 2008 Aug 1;198(3):444-51.
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