organisation - the Instituto Gulbenkian de Ciência

One manuscript summarizes results obtained in 2011:
Fas Signalling and Macrophage-Derived HGF Induce Hepatocyte Apoptosis in
Response to Plasmodium Liver Stage Infection. (Submitted).
MALARIA IMMUNOGENETICS
This project aims to identify genetic and immunological components in clinical
and asymptomatic malaria infections by interrogating human sample collections
from Angola and the Island of Principe.
In the Angola collection malaria cases will be compared will healthy controls and
with relatives to identify genetic variants controlling different clinical forms of
severe malaria. The Island of Principe covers approximately 142 square kilometres
with only about 6000 inhabitants and little emigration. We collected
samples from a total of 1867 healthy individuals in 10 different localities in
Principe in the years 2004, 2005 and 2008. This may represent one of the very
few examples of a whole-population based study in malaria. We found out that
in 2005, while the disease coursed at the mesoendemic level, 20% of the apparently
healthy individuals were infected with Plasmodium. We aim to use this
collection to identify genetic factors that are determining the non-symptomatic
carrier status.
One manuscript summarizes results obtained in 2011:
Involvement of IFNAR1 in cerebral malaria reveals a pathogenesis mechanism
dependent on CD8+ cells (Submitted).
B1 CELLS AND NATURAL ANTIBODIES IN TYPE 1 DIABETES (T1D) PATHOGENESIS
Type-1 diabetes (T1D) is generally known as a T-cell mediated autoimmune disease
where the pancreatic β-cells are destroyed and insulin secretion abrogated.
Yet, B lymphocytes were proven necessary in disease pathogenesis and
the detection of autoantibodies to Beta-cell antigens are one of the earliest indicators
of disease. We propose that autoreactive natural antibodies (NAbs) act
as effector molecules that fuel the autoimmune process through complement
system activation, increased antigen presentation to T cells and/or autoreactive
B cell proliferation in the pancreatic lymph nodes. By exploring on one hand the
involvement of B1 cells and in particular autoreactive NAbs in T1D pathogenesis
and on the other hand the genetic factors determining the dysfunctions in this
cell compartment, we will be able to uncover the missing links. This project will
elucidate mechanisms that link early B1 cell development to autoantibody secretion
and to T1D pathogenesis in murine and human disease.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
56