Targeting Extracellular DNA Traps in an Experimental Cerebral Malaria Model

Malaria is a public health threat, with an estimated 249 million cases and 608000 deaths occurred in 85 malaria-endemic countries in 2022.¹ A large proportion of these deaths are caused by cerebral malaria (CM), which is characterized mainly by cerebrovascular dysfunction.² Infection of C57Bl/6 mice with Plasmodium berghei ANKA (PbA) results in the development of experimental CM (ECM), which recapitulates many of the features of CM in humans.³ Evidence of neutrophil extracellular traps (NETs) production in samples from patients with malaria has already been observed in the literature.⁴ However, the mechanisms and consequences of NETs formation in MC have not yet been clarified. Thus, the aim of this study is to investigate the role of extracellular DNA traps in clinical and pathological features in an ECM model. Male C57Bl/6 mice (6 weeks) were infected with 1x10⁶ PbA-infected red blood cells intraperitoneally and treated every 12 hours for 6 days intraperitoneally with saline, pulmozyne (PMZ)(5mg/kg), N-AcetylHeparin (NAH)(10mg/kg) and both. This study was approved by CEUA with identification protocol no. 139/22. To evaluate the treatments, total leukocyte quantification and identification in the blood were performed, as well as analysis of peripheral parasitemia, SHIRPA protocol, pulmonary edema and Evans Blue dye assay and we observed an increasing trend in most of these parameters in mice infected with PbA and treated with PMZ and PMZ+NAH. In addition, bone marrow lavage was performed and we observed a tendency for a decrease cellularity and number of neutrophils in mice infected with PbA and treated with PMZ or PMZ+NAH, compatible with the tendency to increase cellularity in the blood. In general, our results showed a tendency for increased disease severity in mice infected with PbA and treated with PMZ and PMZ+NAH.

1 Lancet Microbe. (2024) Mar;5(3):e214

2 Front Immunol. (2018) Sep 10;9:2016

3 Infect Immun. (2008) Jul;76(7):3312-20

4 Malar J. (2008) Feb 29;7:41