Cutting-edge technology has resulted in a groundbreaking discovery in comprehending the immune response to malaria re-infection. Scientists at the Doherty Institute have found that the reaction of vital immune cells to malaria parasites varies significantly upon re-infection. This breakthrough has critical implications for the battle against malaria, especially for children residing in highly endemic regions.
In 2022, malaria has been a substantial cause for concern, with over 600,000 deaths reported in 85 countries. It is distressing that 95% of these deaths occurred in the African region, with 80% being children under the age of five, who are particularly susceptible to multiple infections.
Repeated infections eventually lead to partial immunity, but the effects on different immune cells, particularly CD4+ T cells, have remained largely unknown. These cells play a crucial role in orchestrating the body’s immune response to protect against malaria infection and re-infection.
In a study published in Nature Communications, researchers utilized single-cell and spatial transcriptomics, as well as machine learning methods, to closely observe CD4+ T cells in the spleen, a vital organ in the immune response, during re-infection with malaria parasites.
Spatial transcriptomics, also known as tissue genomics, provides a detailed map of cells within body tissue, revealing that CD4+ T cells occupied distinct areas of the spleen before re-infection.
Professor Ashraful Haque of the University of Melbourne, who is also the Laboratory Head at the Doherty Institute and senior author of the study, explained that some CD4+ T cells responded vigorously during re-infection, while others appeared to have no response at all.
The study unveiled a phenomenon in which T cells that responded well during the first infection made either a strong, moderate, or no response during the second infection. This previously undiscovered diversity in the immune response offers valuable insights into how children, who frequently experience multiple severe malaria infections, may react during these periods.
The researchers also found that CD4+ T cells responsible for guiding antibody production remained focused on their task despite the distraction of a new infection. Other CD4+ T cells, believed to retain memory of the first infection, responded rapidly in a way that was almost identical to the first response.
These findings highlight the complexity and sophistication of the immune response to malaria. The researchers believe that the immune system is capable of protecting immune cells during re-infection, allowing them to continue instructing the body’s antibody factory, known as B cells, to produce antibodies.
A study published in Cell Reports by the same team of researchers detailed how spatial transcriptomics and computer science can be utilized to locate immune cells in tissues, providing insights into how cells might interact with each other.
The researchers believe that spatial transcriptomics not only offers hope for a better understanding of malaria but also has the potential to revolutionize how diseases affecting human tissues are diagnosed and treated, ultimately saving lives and improving health outcomes for children and adults worldwide.
The discovery has laid the groundwork for future research to delve into the detailed molecular pathways and cellular interactions that control CD4+ T cell function in malaria. This knowledge could lead to new interventions that enhance the immune system’s ability to combat this deadly disease.
The study was peer-reviewed and published in Nature Communications. It was a collaboration between the University of Melbourne and the Broad Institute of MIT and Harvard University and was funded by the National Health and Medical Research Council.