B4 - Regulation of the T cell response during malaria

B4_April 2014

Principal Investigator:
PD Dr. rer nat. Thomas Jacobs
Bernhard Nocht Institute for Tropical Medicine
Department for Immunology
Bernhard-Nocht-Str. 74
20359 Hamburg
Phone: +49-40-42818-535
Fax: +49-40-42818-400
E-Mail: tjacobs@bni-hamburg.de

Project description

The immune response during malaria can provide protection but an over-activation can induce pathology and is associated with a severe outcome of disease.

Mechanisms that regulate the immune response are not well understood. An effective balance between pro- and anti-inflammatory responses is established only after a serious of malaria episodes. Especially in children an overwhelming response can lead to cerebral malaria that ends often fatal. A better understanding of immune regulation provides new strategies for specific therapeutic intervention.

B4 in 60 SecondsVideoarchiv

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Our results from the first funding period demonstrate that the expression of the co-inhibitory molecule BTLA dampens the immune response during malaria. BTLA not only inhibits T cells but also B cells and cells belonging to the innate immune system. In addition we found that the efficacy of vaccines against the liver-phase can be prolonged by repeated challenge with the pathogen.

During the present funding period we want to understand how co-inhibitory molecules modulate the immune system and how we can manipulate these pathways to improve protection. New findings derived from malaria models will be studied in parallel in human malaria samples.

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Mackroth MS, Abel A, Steeg C, Schulze Zur Wiesch J, Jacobs T

Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function
PLoS Pathog. 2016 Nov 1;12(11):e1005909. doi: 10.1371/journal.ppat.1005909.

Sellau J, Alvarado CF, Hoenow S, Mackroth MS, Kleinschmidt D, Huber S, Jacobs T

IL-22 dampens the T cell response in experimental malaria
Sci Rep. 2016 Jun 17;6:28058. doi: 10.1038/srep28058.

Lapke N, Tartz S, Lee KH, Jacobs T

The application of anti-Toso antibody enhances CD8 T cell responses in experimental malaria vaccination and disease
Vaccine. 2015 Nov 27;33(48):6763-70. doi: 10.1016/j.vaccine.2015.10.065. Epub 2015 Oct 25.

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