Figure 2:

Summary of findings. Infection with PccAS or PbA malaria parasites in C57BL/6 mice leads to divergent outcomes, which can be reversed by disrupting inflammatory responses. The C57BL/6 mice are resistant to PccAS infection (left panel); the mice show symptoms of malaria but control parasite burden and survive. However, in Irak4^–/– animals, inflammatory responses to malaria are decreased while parasite loads are increased, a process which may be caused by impaired macrophage function, resulting in reduced survival. When infected with PbA (right panel), C57BL/6 mice generate an excessive inflammatory response, leading to immunopathology and ultimately death of the host. Irak4^–/– animals, by contrast, have ablated malaria inflammatory responses resulting in decreased cerebral pathology, possibly through the expansion of regulatory T cells, and improved survival. Lower levels of inflammatory cytokines generated during malaria infection in Irak4^–/– animals reverses the outcomes of both PbA and PccAS infections. Animals lacking IRAK4 become susceptible to PccAS, but resistant to PbA, supporting our hypothesis that PbA and PccAS reflect a clinical spectrum of disease defined by host response to infection. This figure appears in color at www.ajtmh.org.