gms | German Medical Science

12th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

14.11. - 15.11.2014, Bonn

Doxycycline inhibits experimental cerebral malaria by altering T cell responses and reducing inflammatory mediators

Meeting Abstract

  • Janina M. Küpper - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany
  • Kim E. Schmidt - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany
  • Judith Alferink - Department of Psychiatry and Psychotherapy, University Hospital Muenster, Germany; Institute of Molecular Psychiatry, University Hospital Bonn, Germany
  • Beatrix Schumak - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany
  • Sabine Specht - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany
  • Achim Hoerauf - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany

12th Malaria Meeting. Bonn, 14.-15.11.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14mal25

doi: 10.3205/14mal25, urn:nbn:de:0183-14mal253

Veröffentlicht: 17. Dezember 2014

© 2014 Küpper et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

We investigated the impact of doxycycline treatment on Plasmodium berghei ANKA (PbA) induced experimental cerebral malaria (ECM). The complex inflammatory networks triggered by the parasite leads to the destruction of the blood brain barrier (BBB). Administration of doxycycline prevented neuropathology in PbA infected mice. Local inflammation was reduced to a minimum and BBB damage was prevented.

These effects were still detected when mice were infected with a higher parasite load, equalizing peripheral parasitemia in untreated (normal infection) and treated (high dose infection) mice on day 6 post infection. Other tetracycline derivatives show similar effects, but only those with known immune-regulatory properties.

Our results provide evidence that the inhibition of ECM is to a large extend by anti-inflammatory actions of doxycycline, despite observed anti-parasitic effects.

Analyzing brain tissue by FACS and ELISA, we found that in treated animals, immune cell infiltration was impaired and the generation of inflammatory cytokines like CCL5 and TNF was reduced compared to infected controls. Especially T cells found to be reduced in number and activation. The T cells accumulated in the spleen and despite similar general activation compared to PbA infected controls, these cells showed reduced parasite-specific cytotoxicity after doxycycline treatment, as shown by Granzyme B production and an in vivo kill.

Our results suggest that during ECM in addition to known anti-parasitic effects several systemic and local inflammatory processes are targeted by doxycycline, inhibiting BBB disruption and neuropathology. Thus we provide theoretical support for retaining doxycycline in the treatment of severe human malaria.

Note: The authors Janina M. Küpper and Kim E. Schmidt contributed equally. Sabine Specht and Achim Hoerauf shared the senior authorship.