Laboratory of Parasitic Diseases

Alan Sher, Ph.D., Chief

Thomas Nutman, M.D., Deputy Chief

The Laboratory of Parasitic Diseases (LPD) conducts basic and applied research on the prevention, control, and treatment of a variety of parasitic and bacterial diseases of global importance. The work of the group is largely directed toward the identification of immunological and molecular targets for disease intervention. The pathogens studied include parasitic protozoa (Leishmania, Toxoplasma, Giardia, Plasmodium, Trypanosoma cruzi, Cryptosporidium, Entamoeba) and helminths (Filariae, Schistosoma, Strongyloides, Taenia) as well as non-parasitic agents (e.g., mycobacteria). Much of this work is directed at uncovering basic aspects of the host-pathogen interaction in both humans and experimental animal models as well as in the invertebrate vectors that transmit medically important parasites. The LPD also includes a clinical group that conducts patient-centered research at the NIH Clinical Center as well as international field studies in India, Latin America and Africa. A new focus is on food- and water-borne protozoa that represent possible bioterrorism threats.

In recent work, LPD researchers

• Demonstrated that IL-10-producing natural regulatory T cells (Treg) control persistent Leishmania major infection in the skin and that Treg that accumulate at sites of parasitic infection can recognize microbial antigens
• Showed that the CD8+ T-cell response to leishmania antigens is strictly TAP and proteosome independent, and that leishmania inhibit the more efficient, ER based cross-presentation pathway in DC
• Identified a galectin-like molecule in cDNA libraries of sand flies that controls leishmania promastigote-midgut attachment and species-specific vector competence
• Identified and characterized a secretory chitinase that facilitates leishmania parasite infection/survival in its insect vector and characterized a novel kinesin motor protein involved in parasite division/multiplication
• Identified IL-13 and IL-13 receptors as critical regulators of fibrosis in schistosomiasis and demonstrated that this pathogenic response is completely TGF-ß independent
• Showed that IL-21/IL-21R signaling is an important co-factor in the development of alternatively activated macrophages which regulate type-2 immunity
• Demonstrated that filarial antigens alter both dendritic cell and T- cell responses to Mycobacterium tuberculosis
• Identified toll-like receptors (TLR) on human T cells and demonstrated that patent filarial infections modulate their expression
• Showed that basophils are the major source of IL-4 in chronic human helminth infections and thereby contribute to the maintenance of the worm-induced Th2 response
• Identified a new subgroup of hypereosinophilic patients and described a novel strategy for treating them
• Characterized the phenomenon of perilesional edema associated with calcified granulomas in neurocysticercosis and its role in causing seizures in this population
• Established roles TLR signaling in host resistance to Toxoplasma gondii and mycobacteria and identified toxoplasma profilin as the major ligand recognized by TLR11 and principal agonist for IL-12 induction in this apicomplexan protozoan
• Demonstrated a major function for the interferon-inducible GTPase LRG47 in the regulation of the hematopoietic response to bacterial and protozoan infection

Office of the Chief

Cell Biology Section

Dennis M. Dwyer, Ph.D.

Gastrointestinal Parasites Section

Theodore E. Nash, M.D.

Helminth Immunology Section

Thomas B. Nutman, M.D.

Immunopathogenesis Section

Thomas A. Wynn, Ph.D.

Immunobiology Section

Alan Sher, Ph.D.

Intracellular Parasite Biology Section

David L. Sacks, Ph.D.

Molecular Parasitology Unit

Michael Grigg, Ph.D.

Mucosal Immunology Unit

Yasmine Belkaid, Ph.D.

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