The Potential Role of Monocyte-Derived Macrophages in Preventing Malarial Parasitemic Recrudescence in a Mouse Model

Frequent recrudescence is responsible for persistent Plasmodium infection after the acute stage. Our previous study demonstrated that phagocytic cells are essential for controlling Plasmodium chabaudi chabaudi AS (P. chabaudi) recrudescence. Nevertheless, the specific type of phagocytic cells involved in controlling P. chabaudi recrudescence, as well as their underlying molecular mechanisms of action, remain elusive. Herein we employ single-cell RNA sequencing (scRNA-seq) to analyse splenic phagocytic cells during both the acute and recrudescent phases of P. chabaudi infection. Using scRNA-seq, we found that monocyte-derived macrophages (MDMs) declined during the acute stage of P. chabaudi blood-stage infection, and then expanded rapidly in the recrudescence stage. The changing trend of MDMs was confirmed by flow cytometry. To explore the potential role of MDMs in controlling parasitemic recrudescence, MDMs were reduced by a low dose of clodronate liposomes (CLs) during the recrudescence stage, which significantly elevated the P. chabaudi parasitemia. Additionally, no significant difference in the proportion of splenic MDMs or classical monocytes (CMs) within the monocyte population was observed between the infected CCR2^-/- mice and their control littermates, suggesting that the transition from CMs to MDMs may not occur in this model. The results indicate that MDMs potentially play a protective role in preventing malarial parasitemic recrudescence, offering valuable insights into immune-based interventions against Plasmodium infection and potentially contributing to the prevention of malaria transmission.