Research Group Heussler (Malaria I) - Bernhard-Nocht-Institut für ...

Medical Microbiology Section
Chairman‘s Summary
The Medical Microbiology Section combines the Departments
of Immunology, Virology, and Helminthology,
the Central Diagnostic Unit and the animal facilities.
Selected projects are described in the following reports.
The Department of Immunology is mainly concerned
with the immune response against parasites but also
performs work in basic immunology. Investigations on
the role of T cells in malaria show a dichotomy between
immunopathogenetic influence and protective function.
The role of NK cells and of cytokines of the innate immune
system in the immune defence against Trypanosoma
cruzi are investigated and genetic loci determining
resistance to experimental Chagas’ disease are
identified. The unknown function of the CD83 molecule,
a member of the immunoglobulin superfamily, is analysed.
Transgenic mice were generated in which either
the CD83 immunoglobulin fusion protein is secreted by
MHC class II positive cells or the CD83 molecule is expressed
under the control of the MHC class I promotor.
Both of these types of mice have interesting phenotypes
indicating that CD83 in fact is important for T cell
ontogeny and activation. How heat shock proteins can
act as danger signals in the immune system is investigated.
Research in the Department of Virology is mainly
concerned with haemorrhagic fever viruses. Lassavirus
replication, the epidemiology and pathogenesis of
Lassa fever and novel diagnostic procedures. A new
sero-diagnostic test for Dengue fever was used in Hué,
Vietnam, for epidemiological investigations. The RNA
helicase complex of Flaviviruses and Arenaviruses was
investigated with respect to sensitivity to different lead
substances with the aim of defining new inhibitor molecules.
The role of glycosylation of the V3 loop of HIV-1
gp120 protein for the effectivity of neutralizing antibodies
is investigated in a collaborative project at the University
of Hamburg. In addition to the well established
PCR-methods to detect Lassa, Ebola and Marburg viruses
(including all substrains), new real-time PCRs were
developed and validated for a number of tropical viruses.
The Department of Virology received high public attention
due to its taking part in the identification of the
SARS virus. Several cases with virus-induced acute haemorrhagic
fever (VHF) in Germany and other European
Countries. For these patients an emergency diagnostic
procedure had to be established. On average a
final result is obtained within 6 hours after arrival of the
Medical Microbiology Section
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blood specimens in the L4 laboratory. A 24 h emergency
hotline is installed and can be reached day and
night via 0049-40-42818-0. Since the biosafety level 4
containment laboratory of the Department now has
been operating without difficulties for more than 20
years, experts from several other European countries
came to obtain advice about construction and maintaining
of such a laboratory.
The Department of Helminthology concentrated on
filariasis research. The department had performed work
on the immune mechanisms active against filaria in a
mouse model (infection of BALB/c mice with Litomosoides
sigmodontis, that allows the development of
microfilaria producing worms from infective larvae).
This model was used to identify the interactions of cytokines
and effector cells and also to prove the importance
of Wolbachia endosymbionts for fertility and survival
of the worms. This has led to the identification of a
new treatment strategy using antibiotics to target the
endobacteria. Clinical studies in Ghana and India are
performed that show that depletion of endobacteria
from O. volvulus lead to longterm depletion of microfilaria
due to filaricidal effects on adult worms in onchocerciasis
and lymphatic filariasis. In onchocerciasis, the investigation
of the T cell response of patients with the
generalized form of the disease has led to the identification
of regulatory T cells that are responsible for the
specific immunosuppression in these patients. ue to
the leave of Dr. Achim Hoerauf to the University of
Bonn the Department will not be continued in its present
form but (a) research group for helminthology will
be established to continue filariasis research.
The Central Diagnostic Unit consists of combined laboratories
from the Departments of Immunology, Virology
and Molecular Parasitology. It performs the direct
identification of parasites, bacteria and viruses by
microscopy, cultivation and molecular detection tests
as well as the serodiagnosis of parasitic, bacterial and
viral infections. New diagnostic methods developed by
the research laboratories are evaluated and eventually
incorporated into the diagnostic routine.
Since 2002 the Central Diagnostic Unit is appointed
by the Federal Ministry of Health as the National Reference
Centre for Tropical Infections. Because of its specialization
the Unit receives material submitted from all
parts of Germany and also from Denmark and Austria.
In 2003 a research group for molecular diagnostics
headed by Dr. Christian Drosten was established that
works on molecular methods to widen the spectrum of
diagnostic procedures to other rare infectious agents
such as microsporidia, trypanosomes, rickettsia and several
fever viruses.
Experimental investigations in animals are an essential
component of research in Tropical Medicine. Cer-