- A research team
Wellcome Trust Sanger Institute has identified the pathway that T cells
choose in fighting malarial infection.
- Activation of the
gene Galectin 1 has been found to increase the production of T cells
- The study
identifies Galectin 1 as a potential target for drug therapy against
research team has identified, for the first time, the mechanisms that immature
T cells choose to fight against malarial infection. The study that involved tracking each T cell during the onset of
malarial infection was conducted by a research team from the Wellcome Trust
Sanger Institute which was published in the journal Science Immunology.
There was a whole network of chemical pathways
that occurred between the various cell types to result in specialized T cells
genomics technology as well as computational modeling were used to ascertain
which genes were involved in the production of T cells against a malarial
infection. When the gene Galectin 1 was activated, it lead to the production of
a specific type of T cells, highlighting the possible use of this gene as a
target for drug therapy against malaria and other associated infections.
‘Activation of Galectin 1 Gene Could Hold The Key to Better Immune Response Against Malaria.’
T Cells and Immunity
The host defense against an infection is
complex, with specialized T cells that form to fight against specific immune
cells. There are two types of T cells that are generally formed to fight
against infections and they include
- T helper1 (Th1)
- T follicular
current study found that the activation of the Galectin 1 gene resulted in the
production of more number of Th1 cells. These cells were important in the
removal of the parasite from the blood and are necessary during the early stages
of the infection while in the later stages or for long term immunity more Tfh
cells are needed.
co-lead author of the study, Dr Ashraful Haque, from the QIMR Berghofer Medical
Research Institute, Brisbane, Australia, said that this is the first study to
identify that activation of the Galectin 1 gene was shown to activate Th1
production. This further highlighted the potential use of the gene as a
therapeutic target for malarial infection. There were other genes that were
identified in the study and the scientists are keen on identifying if the
activation of these genes could further enhance the immune response of the host
against malarial infection.
Mechanism of Conversion
molecules that are involved in the conversion of T cells into other forms are
not well understood. In the current study, the scientists utilized single cell
RNA sequencing which aided in obtaining insights into genes that were active in
each T cell in mice with malaria. The various stages of the T cells, from
immature T cells into Th1 or Tfh could be tracked using this method.
co-author of the study who is also the Head of The Cellular Genetics at the
Sanger Institute, Dr. Sarah Teichmann said that these were the first high
resolution images of cells that were being monitored over a period of time
using a pathogen in mice. The latest advancements in genomics along with
computational methods were utilized in the reconstruction of how the cells
modify in response to malarial infection. The co-author stated further that the
advancements in technology allowed better understanding of complex processes.
GPfates- Computational Modeling System
research team devised GPfates, which is a new computational modeling system
that allows scientists to visualize how cells communicate with each other. This
tool utilized the spatio-temporal statistics to determine which genes were
activated in the different T cell types.
other co-author of the study, Dr. Oliver Stegle, from the European
Bioinformatics Institute, said that genomics was utilized to identify
inter-cellular conversations that occurred between immune cells like monocytes
as well as Th1 cells. According to Dr. Oliver, this was the first time that the
data was utilized to identify numerous new genes which are associated with the
production of antibodies.
activation of these genes are critical to the health of the individual, as it
can produce two diverse effects; on the one hand it could aid in fighting the
infection and on the other it could lead to tumor progression. The computational
tool that was designed by the scientists involved in the study may be used by
other scientific studies conducted to understand cellular pathways.
Regulation of T Cell Function by Galectin
has been known to regulate the function of the T cells, as detailed in the
study published in the journal Immunological Reviews
, titled "Galectin-3
regulates T-cell functions" by Dr. Hsu DK and colleagues from The Department of
Dermatology, University of California, USA.
study found that in resting CD4+ and CD8+ T cells, Galectin-3 was absent but it
could be induced by some of the mechanisms including
- viral trans
- T-cell receptor
is expressed in T cells as well as CD4+ memory T cells. There are extracellular
functions that are associated with
- lectin activity
- recognition of
functions of this protein in the T cells include
- inhibition of
- induction of cell
- regulation of TCR
is increased interest being shown by the scientific community in galectin
research, as it has identified galectin-3 protein as a key regulator in T-cell
functions. The current study that showed that an activation of galectin gene
results in the production of specialized T cells has highlighted its potential
use as a target for drug therapy against malaria infection.
- Galectin-3 regulates T-cell functions - (https://www.ncbi.nlm.nih.gov/pubmed/19594632)