Gene Target for Immune Cell Activation Against Malaria Identified

Gene Target for Immune Cell Activation Against Malaria Identified

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Highlights:
  • 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
A 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 against malarial infection.
Gene Target for Immune Cell Activation Against Malaria Identified

Galectin 1

Single-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 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 helper (Tfh)
The 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.

The 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

The 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 System

The 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 Galectin

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.

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
Galectin is expressed in T cells as well as CD4+ memory T cells. There are extracellular functions that are associated with
  • lectin activity
  • recognition of matrix glycans
The functions of this protein in the T cells include
  • inhibition of apoptosis
  • induction of cell growth
  • regulation of TCR signal transduction
There 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.

References:
  1. Galectin-3 regulates T-cell functions - (https:www.ncbi.nlm.nih.gov/pubmed/19594632)
Source: Medindia

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