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Viktor S Zenkov, Vitaly V Ganusov, James O'Connor, Ian A Cockburn, Activated Plasmodium-specific CD8 T cells find liver stages mostly randomly, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 122.1, https://doi.org/10.4049/jimmunol.202.Supp.122.1
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Abstract
Malaria is a major infectious disease, with 500,000 people dying every year. Malaria infection starts when an infected mosquito injects malaria sporozoites during feeding which migrate to the liver and form liver stages. Elimination of liver stages is a major feature of CD8 T cell-based malaria vaccines. It is established that vaccines inducing high numbers of memory CD8 T cells are capable of eliminating all liver stages, preventing clinical malaria. However, how CD8 T cells are capable of doing that in the 48-hour liver stage in mice remains unclear. One possibility is that as sporozoites invade hepatocytes from the blood, they induce local inflammation, acting as an attraction signal for T cells. We performed experiments in which fluorescent-labeled Plasmodium sporozoites and Plasmodium-specific and non-specific CD8 T cells were tracked in mouse livers using intravital microscopy. To analyze the data we used three metrics to measure attraction of T cells to the infection site based either on angles or distances from a T cell to the parasite. We found that for the majority of imaged T cells, there is no evidence of attraction to the parasite, indicating that in this experimental system, vaccine-induced CD8 T cells locate the infection site randomly. By modeling T cells searching for the infection site and utilizing experimentally measured speeds of T cell movement in the liver, we found that if enough memory CD8 T cells are present in the liver, all parasites can be found within 48 hours after sporozoite injection. Taken together, our results suggest that memory CD8 T cells in the liver perform the search for infection randomly, precluding the need to find specific signals and receptors of T cell attraction to the infection site.
