Abstract

In the US, Toxoplasma gondii is the second leading cause of food borne mortality and more than 60 million people are persistently infected with this organism and this infection is a concern in many patients with primary or acquired defects in T cell mediated immunity. Due to the ease of transmission and its ability to cause severe disease, T. gondii is classified as a Class B Biodefense pathogen. The ability to balance the development of protective and pathological immunity is key in determining the outcome of this infection. This proposal studies the role of the cytokine IL-27 in controllinga unique population of regulatory T cells to limit inflammation and is broadly applicable to understanding how this cytokine may be useful as a therapy.

Public Health Relevance

Toxoplasma is a common opportunistic infection in patients with defects in T cell function and can cause significant disease in immune competent individuals. The ability to control the inflammatory response to this infection is essential to limt collateral damage and key to host cell survival. The overall goal of this proposal is to understand how the cytokine IL-27 controls the inflammatory response with the overarching goal of developing therapies that are useful to modulate the immune system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI110201-01
Application #
8657334
Study Section
Special Emphasis Panel (ZRG1-IMM-N (03))
Program Officer
Lapham, Cheryl K
Project Start
2013-12-01
Project End
2018-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$360,000
Indirect Cost
$135,000

  Institution

Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

DeLong, Jonathan H; Hall, Aisling O'Hara; Konradt, Christoph et al. (2018) Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1. J Immunol 200:1761-1770
Konradt, Christoph; Hunter, Christopher A (2018) Pathogen interactions with endothelial cells and the induction of innate and adaptive immunity. Eur J Immunol 48:1607-1620
O'Brien, Carleigh A; Overall, Christopher; Konradt, Christoph et al. (2017) CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection. J Immunol 198:4054-4061
Muallem, Gaia; Wagage, Sagie; Sun, Yan et al. (2017) IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection. PLoS Pathog 13:e1006173
Glatman Zaretsky, Arielle; Konradt, Christoph; Dépis, Fabien et al. (2017) T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow. Cell Rep 18:1906-1916
Klein, Robyn S; Hunter, Christopher A (2017) Protective and Pathological Immunity during Central Nervous System Infections. Immunity 46:891-909
Silver, Jonathan S; Kearley, Jennifer; Copenhaver, Alan M et al. (2016) Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs. Nat Immunol 17:626-35
Pritchard, Gretchen Harms; Cross, Eric W; Strobel, Marjorie et al. (2016) Spontaneous partial loss of the OT-I transgene. Nat Immunol 17:471
Yoshida, Hiroki; Hunter, Christopher A (2015) The immunobiology of interleukin-27. Annu Rev Immunol 33:417-43
Lee, Hyang-Mi; Fleige, Anne; Forman, Ruth et al. (2015) IFN? signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells. PLoS Pathog 11:e1004635

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