- 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 malaria
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
Galectin 1Single-cell 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.
T Cells and ImmunityThe 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 helper (Tfh)
Mechanism of ConversionThe 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.
The 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 SystemThe 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.
The 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.
The 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 GalectinGalectin 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.
The 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 activating factors
- T-cell receptor (TCR) ligation
- calcium ionophores
- lectin activity
- recognition of matrix glycans
- inhibition of apoptosis
- induction of cell growth
- regulation of TCR signal transduction
- Galectin-3 regulates T-cell functions - (https://www.ncbi.nlm.nih.gov/pubmed/19594632)