B4 - Regulation of the T cell response during malaria


Principal Investigators:
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

Dr. med. Maria Sophia Mackroth
University Hospital Hamburg-Eppendorf
I. Medical clinic and policlinic
Martinistr. 52
20246 Hamburg
E-Mail: m.mackroth@uke.de

Participating staff:

Steeg – MTA
Hüsing – MTA
Dr. rer. nat. Riehn – PostDoc
Lea Kaminski – PhD student

Project description

In the course of malaria, the immune response can slow down the multiplication of plasmodia. However, activation which is too string, leads to a pathology and can trigger a life-threatening course of the disease. An effective balance between pro- and anti-inflammatory immune response develops after many malaria diseases.

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In the first two funding periods we were able to show that the blood phase of malaria is associated with a strong induction of co-inhibitory molecules such as CTLA4, PD1, BTLA, LAG3, TIGIT on T cells that modulate the immune response. Children with severe malaria show a higher expression of co-inhibitory molecules than children with uncomplicated malaria. Interestingly, cells with high expression of co-inhibitory molecules inhibit other T cells; they act like regulatory T cells (Tr1 cells). On the one hand, this inhibitory effect may have a protective effect, in which a stronger inflammation with a more severe course of the disease is prevented. On the other hand, however, this can also have a negative effect on the development of a protective immune response.

The current funding period therefore focuses on a more detailed study of the regulatory T cells (Tr1 cells) induced during acute malaria. Furthermore, the effect of these regulatory T cells on the malaria-specific T cell response to the liver phase of malaria during and after an infection should be investigated. The studies will be carried out in experimental malaria models in the mouse, as well as in travelers with malaria and in a cohort study in Ghana.

Related News

Abel A, Steeg C, Aminkiah F, Addai-Mensah O, Addo M, Gagliani N, Casar C, Yar DD, Owusu-Dabo E, Jacobs T, Mackroth MS.

Differential expression pattern of co-inhibitory molecules on CD4+ T cells in uncomplicated versus complicated malaria
Sci Rep. 2018 Mar 19; 8 (1) : 4789

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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