Plasmodium berghei ANKA infection elicits a mast cell response in mice that are susceptible to experimental cerebral malaria

Mast cells are tissue resident granulocytes present in several barrier organs, including the skin, where the natural malaria infection occurs, and the peritoneal cavity, which is the preferred route of infection in the murine cerebral malaria (CM) model, and thus are among the first cells to interact with the parasite at the moment of infection. Patients with complicated severe malaria show increased activation of skin mast cells, and mast cell derived Flt3L positively correlates with increased activation of CD8α⁺ dendritic cells and CD8⁺ T cells, contributing to a worse disease outcome. It is not clear, however, how the peritoneal cavity is affected by the infection in this model, and its correlation to the severity of the disease. Thus, the aim of this work was to understand the role of innate immunity cells in the difference in susceptibility to cerebral malaria between susceptible C57BL/6J mice and resistant BALB/c mice. C57BL/6J and BALB/c mice were infected intraperitoneally with GFP-expressing Plasmodium berghei ANKA. At 5 days post infection (dpi), prior to the onset of the symptoms of cerebral malaria in C57BL/6J mice, both mouse strains showed an increase in systemic inflammation, with increased serum levels of CXCL10. Flow cytometry analysis of spleens of control or infected mice at 5 dpi showed an increase in the activation of CD8⁺ T cells of C57BL/6J mice only, along with an increase in the frequency of CD8α⁺ dendritic cells. Flow cytometry analysis of the peritoneal cavity of control or infected mice at 5 dpi showed a significant increase in the frequency and number of mast cell progenitors in infected C57BL/6J mice, which was not observed on infected BALB/c mice. These data point towards a persistent mast cell response at the site of infection only in mice that are susceptible to CM, which correlates to an increased CD8⁺ T cell response that is associated with a worse outcome of the disease. Financial Support: FAPERJ. CEUA: 027/21 and A38/23-027/21.