Studies on Immune Regulation in Toxoplasmosis

Sher, A.

Abstract

The overall aim of this project is to analyze the immune response to Toxoplasma gondii in order to define which cellular immune components and parasite target antigens are involved in the control of infection and its breakdown in immunocompromised hosts. Progress was made this year in the following areas: A. Demonstration of CD8+ cytolytic activity against T. gondii infected cells. CD8+ cells from vaccinated mice were shown to lyse infected or antigen pulsed macrophages in vitro. An antigenic fraction was partially purified which contains the appropriate target antigens. B. Investigation of T cell subset requirements for reactivation. Reactivation of T. gondii in chronically infected mice was shown to be due primarily to a loss in CD8+ T cell function. C. Establishment of a MAIDS - toxoplasmosis model. Infection of mice with a retrovirus mixture (MAIDS) was shown to reduce susceptibility to challenge infection and cause partial reactivation of latent infection.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000579-02
• Application #: 3803260
• Support Year: 2
• Fiscal Year: 1991

Institution

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

Publications

la Sala, Andrea; He, Jianping; Laricchia-Robbio, Leopoldo et al. (2009) Cholera toxin inhibits IL-12 production and CD8alpha+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function. J Exp Med 206:1227-35

Goldszmid, Romina S; Coppens, Isabelle; Lev, Avital et al. (2009) Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells. J Exp Med 206:399-410

Plattner, Fabienne; Yarovinsky, Felix; Romero, Stephane et al. (2008) Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. Cell Host Microbe 3:77-87

Feng, Carl G; Zheng, Lixin; Jankovic, Dragana et al. (2008) The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death. Nat Immunol 9:1279-87

Jankovic, Dragana; Kullberg, Marika C; Feng, Carl G et al. (2007) Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204:273-83

Amsen, Derk; Antov, Andrey; Jankovic, Dragana et al. (2007) Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 27:89-99

Goldszmid, Romina S; Bafica, Andre; Jankovic, Dragana et al. (2007) TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production. J Exp Med 204:2591-602

Trinchieri, Giorgio; Sher, Alan (2007) Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 7:179-90

Bertholet, Sylvie; Goldszmid, Romina; Morrot, Alexandre et al. (2006) Leishmania antigens are presented to CD8+ T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo. J Immunol 177:3525-33

Collazo, Carmen M; Sher, Alan; Meierovics, Anda I et al. (2006) Myeloid differentiation factor-88 (MyD88) is essential for control of primary in vivo Francisella tularensis LVS infection, but not for control of intra-macrophage bacterial replication. Microbes Infect 8:779-90