Major Areas of Research
- Regulation of the host immune response to parasitic helminth infection (primarily filarial infections and those caused by soil-transmitted helminths)
- Influence of helminth infection on expression of non-parasitic infections, atopy, and asthma
- Molecular characterization of tissue-invasive helminth parasites
- Mechanisms of eosinophil activation and eosinophilia
- Control of immediate hypersensitivity reactions
- Clinical definition and pathogenesis underlying parasitic diseases
- New therapeutic interventions and methods of diagnosis in parasitic infections
The focus of the Helminth Immunology 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 work focuses on both the host response to helminth infection and the molecular basis for parasitism in helminths and the prototypical responses they induce.
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 1) functional mapping of the earliest host-parasite interaction that influences the polarized immune responses that are the hallmarks of these infections; 2) genomic and proteomic definition of each of the filarial parasites to identify parasite-encoded therapeutic, diagnostic, and vaccine-related targets; 3) studies of pathogenesis underlying disease manifestations (e.g., elephantiasis) in filarial infections; 4) studies of immunologic bystander effects of chronic helminth infection on non-parasitic infections (HIV, tuberculosis, malaria), atopy, and autoimmune diseases; 5) the regulation of igE and eosinophilia in the context of human helminth infections.
The Clinical Parasitology Section is an interdisciplinary group of clinically trained LPD staff members who oversee the clinical research portfolio ad provide clinical care, consultations, and training in tropical medicine and parasitology.
The overriding goals of this program are
- To gain insight into the clinical syndromes associated with parasitic infections
- To understand and help define the pathogenesis underlying clinical disease
- To identify better ways of treating individual infections and to prevent secondary consequences of treatment
- To develop better diagnostic tools for the species-specific diagnosis of active parasitic infection
Although the section has protocols to see patients with any parasitic infection, the majority of patients have neurocysticercosis, filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis), strongyloidiasis, hookwork infections, ascaraisis, giardiasis, echinococcosis, and leishmaniasis. We occasionally see patients with gnathostomiasis, African trypanosomiasis, Chagas disease, and malaria, among others.
Dr. Nutman received his A.B. from Brown University and his M.D. from the University of Cincinnati College of Medicine. He did an internal medicine residency at New York University (Bellevue) and postdoctoral training in the Laboratory of Parasitic Diseases (LPD). He is board certified in internal medicine and allergy and immunology. He also holds a diploma/certificate in tropical medicine and travelers’ health. He has been at NIH in the Laboratory of Parasitic Diseases since 1982, where he is currently deputy chief, as well as chief of both the Helminth Immunology Section and the Clinical Parasitology Section. In addition, he is the director of the NIAID International Center for Excellence in Research (ICER) located in Chennai, India, as well as director of the filariasis unit at the NIAID ICER in Mali. He is on numerous advisory committees and editorial boards and holds patents related to parasite diagnosis and vaccine development. He is the author or coauthor of over 500 papers and book chapters and has received multiple awards for his work in tropical medicine and immunology.
D'Ambrosio MV, Bakalar M, Bennuru S, Reber C, Skandarajah A, Nilsson L, Switz N, Kamgno J, Pion S, Boussinesq M, Nutman TB, Fletcher DA. Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. Sci Transl Med. 2015 May 6;7(286):286re4.
Chatterjee S, Clark CE, Lugli E, Roederer M, Nutman TB. Filarial infection modulates the immune response to Mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells. J Immunol. 2015 Mar 15;194(6):2706-14.
O'Connell EM, Bennuru S, Steel C, Dolan MA, Nutman TB. Targeting Filarial Abl-like Kinases: Orally Available, Food and Drug Administration-Approved Tyrosine Kinase Inhibitors Are Microfilaricidal and Macrofilaricidal. J Infect Dis. 2015 Sep 1;212(5):684-93.
Herrick JA, Metenou S, Makiya MA, Taylar-Williams CA, Law MA, Klion AD, Nutman TB. Eosinophil-associated processes underlie differences in clinical presentation of loiasis between temporary residents and those indigenous to Loa-endemic areas. Clin Infect Dis. 2015 Jan 1;60(1):55-63.
Santiago Hda C, Ribeiro-Gomes FL, Bennuru S, Nutman TB. Helminth infection alters IgE responses to allergens structurally related to parasite proteins. J Immunol. 2015 Jan 1;194(1):93-100.
Desjardins CA, Cerqueira GC, Goldberg JM, Dunning Hotopp JC, Haas BJ, Zucker J, Ribeiro JM, Saif S, Levin JZ, Fan L, Zeng Q, Russ C, Wortman JR, Fink DL, Birren BW, Nutman TB. Genomics of Loa loa, a Wolbachia-free filarial parasite of humans. Nat Genet. 2013 Apr 26;45(5):495-500.
Patents & Clinical Trials
Nutman TB, Fink DL, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Rapid molecular assays for specific detection and quantitation of Loa loa microfilaremia. U.S. application 61/410,232. 04 Nov 2010.
Nutman TB, Fink DL, Burbelo PD, Kubofcik J, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Diagnostic assays and methods of use for detection of filarial infection. U.S. application 61/410,239. 04 Nov 2010.
Nutman TB, Abraham D, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Vaccine and methods of use against Strongyloides stercoralis infection. World patent WO/2011/097216. 11 Aug 2011.
Lazzerio MESL, Nutman TB, Weiss N, inventors; The United States of America, assignee. Nucleotide molecule encoding a specific Onchocerca volvulus antigen for the immunodiagnosis of onchocerciasis. United States patent US 5,416,009. 16 May
Dr. Nutman works on a number of clinical trials with the Clinical Parasitology Section.