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. A common theme in many of the LPD’s research projects is the regulatory environment induced in chronic parasitic and bacterial infection and the identification of determinants of host resistance and pathology.

The LPD also includes a clinical group that conducts patient-centered research at the National Institutes of Health Clinical Center as well as international field studies in India, Latin America, and Africa. Three new programs focus on genetic determinants of virulence in apicomplexan protozoa, the function of the eosinophil in human infectious and inflammatory disease processes, and the role of commensal microbiota in immune regulation and homeostasis.

In recent work, LPD researchers

• Demonstrated a Leishmania sexual cycle during parasite development in the sand fly vector
• Employed in vivo imaging to demonstrate that neutrophils rapidly recruited to the sand fly bite site are the first cells to take up Leishmania in the skin and that they promote the establishment of infection and compromise the efficacy of experimental vaccines
• Identified a new mechanism of pulmonary fibrosis regulated by IL-1 beta and IL-17
• Showed that the suppression of Th2 cytokine-driven inflammation and fibrosis is mediated by Arginase-1-expressing macrophages
• Characterized the roles of Relm-alpha and thymic stromal lymphopoietin (TSLP) in helminth-induced Th2-type immunity
• Demonstrated that commensal bacteria are required for induction of effector responses against pathogens at mucosal sites
• Demonstrated that vitamin A metabolite is required to induce regulatory T cells in the gut
• Demonstrated that during lethal infection with an oral pathogen, regulatory T cells are destabilized and can acquire effector T-cell function
• Demonstrated that filarial parasites induce lymphangiogenesis and lymphatic remodeling
• Identified the major role played by CD25(-) adaptive T regulatory cells (aTreg/Tr1) in mediating the IL-10-dependent regulation of both parasite-specific and bystander T-cell responses
• Elucidated the genome of Loa loa and Wuchereria bancrofti, two pathogenic filariae of humans
• Demonstrated the presence of Wolbachia in the filarial nematode Mansonella perstans suggesting it as therapeutic target, leading to identification of doxycycline as the first effective therapy for Mansonella perstans infection
• Characterized the responses to novel targeted therapies in clinically defined subsets of patients with hypereosinophilic syndromes
• Demonstrated that a Leishmania secretory chitinase, LmexCht-1, acts as both a virulence factor in mice and facilitates parasite colonization and transmission in its sand fly vector
• Used molecular characterization of a unique Leishmania secretory nuclease to show that it functions in the essential acquisition of host-derived nucleotides
• Identified the T2 ribonuclease Omega-1 as the schistosome egg component responsible for conditioning dendritic cells (DC) to trigger polarized Th2 responses
• Elucidated endoplasmic reticulum fusion with parasitophorous vacuoles as a mechanism of cross-presentation in Toxoplasma gondii-infected DC
• Identified the respective role of TLR, IL-1R signaling and the inflammasome in host resistance to M. tuberculosis and in the adjuvant activity of the mycobacterial component in Complete Freunds Adjuvant
• Demonstrated that perilesional edema around calcified granulomas due to degenerated Taenia solium cysts occurs in about 50 percent of persons with a history of seizures and calcified lesions due to neurocysticercosis
• Showed that methotrexate can be used as a corticosteroid sparing agent in complicated neurocysticercosis
• Discovered sylvatic clade of Type X Toxoplasma gondii parasites that recently emerged and are flowing from land to sea to infect marine mammals
• Identified non-archetypal strains of T. gondii causing a more severe, atypical form of toxoplasmic retinochoroiditis in otherwise healthy adults
• Did the first structural characterization of major bradyzoite and sporozoite surface adhesins Toxoplasma expresses on parasite stages that establish intestinal infections in susceptible hosts

Office of the Chief

Alan Sher, Ph.D.
Thomas Nutman, M.D.

Cell Biology Section

Dennis M. Dwyer, Ph.D.

Clinical Parasitology Section

Thomas B. Nutman, M.D., Chief
Siddhartha Mahanty, M.D., M.P.H., Assistant Chief

Eosinophil Pathology Unit

Amy D. Klion, M.D.

Gastrointestinal Parasites Section

Theodore E. Nash, M.D.

Helminth Immunology Section

Thomas B. Nutman, M.D.

Immunobiology Section

Alan Sher, Ph.D.

Immunopathogenesis Section

Thomas A. Wynn, Ph.D.

Intracellular Parasite Biology Section

David L. Sacks, Ph.D.

Molecular Parasitology Unit

Michael Grigg, Ph.D.

Mucosal Immunology Section

Yasmine Belkaid, Ph.D.

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