Figure 3
HMGB1 is not necessary or sufficient for the development of severe malaria following Plasmodium berghei ANKA (PbA) infection in the experimental murine model. (A) Kaplan-Meier survival analysis after C57BL/6 mice were infected with 1 × 106Plasmodium berghei-ANKA (PbA) infected erythrocytes. There was no significant difference in survival between mice receiving an HMGB1 neutralizing antibody (2G7) (black circle, solid line), or control IgG2b (grey diamond, solid line) (Log rank test, p = 0.9, median survival = eight days for both groups; n = 20/group) or PBS control (grey x, dashed line) (Log rank test, p = 0.06; n = 15). Data is pooled from two independent experiments. The kinetics of peripheral parasitaemia are shown up to day 9 post PbA infection for anti-HMGB1 2G7 treatment mice and isotype IgG control (B). Results expressed as a percentage of the parasitized erythrocytes (PE) and represent mean + SEM from one representative experiment (n = 10/group). Levels of TNF, IFN-γ, IL-10, IL-12 and MCP-1 were measured in serum collected from naïve, uninfected mice and PbA-infected mice on day 5 pi using the mouse cytometric bead array (C-G). Bars and whisker represent median and interquartile range (IQR). Statistical differences were assessed by Kruskal-Wallis one-way analysis of variance with Dunn’s multiple comparisons test. * indicates a p value of <0.05. Plasma levels of IFN-γ were confirmed by ELISA (H) and statistical difference between anti-HMGB1 2G7 and isotype IgG control was assessed by Mann–Whitney test (ns, p = 0.73). The line represents the median levels of all individual values in the scatter dot plot.