Thymic Atrophy Development in a Non‐Lethal <i>Plasmodium</i> Infection

The thymus is a vital organ for T-cell development that undergoes significant changes during malaria infection, including atrophy and disrupted structure, which weaken immune responses. This study examines the mechanisms behind thymic atrophy during Plasmodium chabaudi AS infection, focusing on cellular and molecular changes across different parasitemia stages. Our results show that thymic atrophy is marked by a substantial decrease in thymus weight and cellularity, especially at 20%-30% parasitemia levels. A significant loss of DP and SP thymocytes mainly causes this atrophy. Histological analysis revealed notable cortical shrinkage and DNA fragmentation in thymic cells, indicating increased apoptosis. Elevated serum cytokines and chemokines, including IFN-γ, TNF-α, IL-6 and CXCL9, were observed throughout the infection, with higher levels correlating with the degree of thymic atrophy. Also, early release of thymocytes into peripheral tissues, especially the spleen, worsened the decrease in thymic cellularity. However, after parasitemia resolved, the thymus recovered, restoring its structure and thymocyte populations. These results highlight the complex interaction between parasite-induced inflammation and immune cell behaviour, suggesting that even though P. c. chabaudi AS infection is not lethal, a prolonged parasitic burden can cause severe thymic dysfunction, possibly impairing immune system function.