Thomas B. Nutman, M.D.

Senior Investigator
Chief, 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 regulation of these responses and their genetic control
• Regulation of human IgG4 and IgE production
• The mechanisms of eosinophil activation and eosinophilia
• The clinical expression, diagnosis, treatment and control of human helminth infections
• The 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 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 LPD, 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 four major themes: definition of clinical syndromes and their underlying pathogenesis, chemotherapy, prevention of post-treatment adverse reactions, and new methods for diagnosis.

Awards

United States Public Health Service Achievement Medal, United States Public Health Service Commendation Medal, United States Public Health Service Outstanding Service Medal, Bailey K. Ashford Medal from the American Society of Tropical Medicine and Hygiene, United States Public Health Service Unit Commendation Medal

Memberships

• Sigma Xi
• Physicians for Social Responsibility
• American College of Physicians
• Union of Concerned Scientists
• American Society of Tropical Medicine and Hygiene
• American Federation of Clinical Research
• American Association for the Advancement of Science
• American Academy of Allergy and Immunology
• American Association of Immunologists
• Clinical Immunology Society
• American Society of Clinical Investigation
• Infectious Diseases Society of America (fellow)
• American Society of Microbiology
• Royal Society of Tropical Medicine and Hygiene

Current Editorial Boards

Experimental Parasitology, American Journal of Tropical Medicine and Hygiene

Research Group Members

Bottom row (left to right): Amy Klion, Roshan Ramanathan, Abhi Kole; Middle row (left to right): Janine Van Lancker, Priyanka Goel, Tom Nutman, Roshanak Semnani, Kawsar Talaat, Princess Ogbogu, Cathy Steel; Top row (left to right): Joe Kubofcik, Siddhartha Mahanty, Sasisekhar Bennuru, Simon Metenou

Selected Publications

(View list in PubMed.)

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. 2006.176:3885-3889.

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. 176: 3248-3256.

Talaat, KR, Bonawitz, RE, Domenech, P, Nutman, TB. Pre-exposure to live Brugia malayi microfilariae alters the innate response of dendritic cells to Mycobacterium tuberculosis. J Infect Dis. 2006.193:196-204.

Mitre, EES, Tuthill, R, Kubofcik, J, Nutman TB. Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections. J Immunol. 2004. 172; 2439–2445.

Semnani, RT, Law, M, Kubofcik, J, Nutman, TB. Filarial-induced immune evasion: Suppression of the infective stage of Brugia malayi at the earliest host parasite interface. J. Immunol. 2004.172: 6229-6238.

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. 2004.103:473-478.

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