Immunoregulation and Immune Recognition in Filariasis and Non-Filarial Diseases

Nutman, T B.

Abstract

The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of tolerance (by clonal deletion.) rather than active suppression. In vitro models of parasite-antigen driven antibody production as well as parasite-specific and HTLV-1 transformed T cell clones have been developed to understand in more detail those mechanisms regulating antibody production (particularly IgG and IgE) in filarial and non-filarial diseases. Recombinant lymphokines and neutralizing antibodies to them have provided additional tools for defining the mediators involved in this regulation. Qualitative analysis of filaria-specific IgE and IgG in loiasis, lymphatic filariasis, and onchocerciasis have indicated patterns of antigen recognition which differ among groups of patients with different clinical manifestations of filariasis. Using these techniques, possible vaccine targets have been identified for use in onchocerciasis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000197-11
• Application #: 3809573
• Support Year: 11
• Fiscal Year: 1990

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Guadalupe, Irene; Mitre, Edward; Benitez, Susana et al. (2009) Evidence for in utero sensitization to Ascaris lumbricoides in newborns of mothers with ascariasis. J Infect Dis 199:1846-50

Babu, Subash; Bhat, Sajid Q; Kumar, N Pavan et al. (2009) Attenuation of toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy. PLoS Negl Trop Dis 3:e489

Babu, Subash; Bhat, Sajid Q; Pavan Kumar, N et al. (2009) Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells. PLoS Negl Trop Dis 3:e420

Babu, Subash; Blauvelt, Carla P; Nutman, Thomas B (2007) Filarial parasites induce NK cell activation, type 1 and type 2 cytokine secretion, and subsequent apoptotic cell death. J Immunol 179:2445-56

Lipner, Ettie M; Gopi, P G; Subramani, R et al. (2006) Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but BCG influences hookworm prevalence. Am J Trop Med Hyg 74:841-7

Talaat, Kawsar R; Bonawitz, Rachael E; Domenech, Pilar et al. (2006) Preexposure to live Brugia malayi microfilariae alters the innate response of human dendritic cells to Mycobacterium tuberculosis. J Infect Dis 193:196-204

Babu, Subash; Blauvelt, Carla P; Kumaraswami, V et al. (2006) Cutting edge: diminished T cell TLR expression and function modulates the immune response in human filarial infection. J Immunol 176:3885-9

Semnani, Roshanak Tolouei; Keiser, Paul B; Coulibaly, Yaya I et al. (2006) Filaria-induced monocyte dysfunction and its reversal following treatment. Infect Immun 74:4409-17

Mitre, Edward; Nutman, Thomas B (2006) Basophils, basophilia and helminth infections. Chem Immunol Allergy 90:141-56

Babu, Subash; Blauvelt, Carla P; Kumaraswami, V et al. (2006) Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J Immunol 176:3248-56