Imtiaz Khan, PhD, professor of microbiology, immunology, and tropical medicine at the George Washington University School of Medicine and Health Sciences, recently received a $2.9 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health to study the relationship between CD4 dysfunction and cerebral toxoplasmosis.
Toxoplasma gondii, an intracellular pathogen that can cause severe neurological complications, is prevalent worldwide. An infection in pregnant women can result in congenital problems in the fetus, and those who are immunocompromised, such as patients with HIV or AIDS, can develop encephalitis, or inflammation of the brain. As with many intracellular pathogens, innate immune responses act as a first line of defense against toxoplasma gondii, but long-term protection against this pathogen is dependent on adaptive immune systems.
“Among adaptive immune systems, CD8+ T-cells are the primary effector cells against the parasite, with CD4 T-cells providing essential help,” Khan said. “Studies from our laboratory have reported that during chronic infection, CD4 T-cells become exhausted or dysfunctional, which deprives CD8 T-cells of factors needed for their maintenance.”
Khan and his team, based on their preliminary data, are hypothesizing that important co-stimulatory modules, like the protein 4-1BB, are downregulated on antigen-specific CD4 T-cells in infected animals.
“We are investigating the mechanism of this down regulation of an important co-stimulatory molecule that apparently leads to CD4 T-cell dysfunctionality in toxoplasma-infected mice,” Khan explained. “We will also evaluate therapeutic strategies to prevent the loss of functionality in these cells.”
The data generated from this research could help in combating the toxoplasma pathogen, providing potential therapeutic relief to immunocompromised individuals.
The NIH grant will run through May 2025.
