Similar findings later revealed that macrophages ingest and kill the parasites [98, 99]. Protective

immunity depended on macrophage activation as well as antibody. Protection against P. chabaudi adami was found to be independent of antibody but critically dependent on spleen T cells [100], and TNF released from endotoxin-induced macrophage activation was shown to be damaging to both lethal and CP-690550 nmr nonlethal P. yoelii parasites [101, 102]. T cells from mice successfully vaccinated against lethal P. yoelii reacted strongly to parasite antigens, with infiltration of mononuclear cells in antigen-challenged pinnae [28]; when the mice were challenged with live parasites, increased homing of mononuclear cells and parasites to the spleen and liver occurred [78]. This T-cell-dependent shift in cell traffic was interpreted to be a cell-mediated immune response against the parasites as they migrated to the

spleen and liver [79]. Macrophage activation was strongest in infections with the nonlethal P. yoelii and P. chabaudi, and significantly weaker in the lethal P. yoelii and P. berghei infections, and vaccination increased activation more with the former than the latter. It appeared that the attraction and stimulation of cytotoxic myeloid cells by T cells play an important part in the protection of vaccinated mice. This DTH T-cell

response was confirmed by the observation that the trapping of parasites, and of both BGB324 cost lymphoid and myeloid cells, in the spleens and livers of vaccinated mice increased shortly after infection [79]. Studies in vitro revealed that spleen- and liver-derived myeloid cells killed lethal P. yoelii parasites in vitro through TNF and hydrogen peroxide-dependent killing mechanisms [103], and macrophages from mice infected with nonlethal parasites and those from vaccinated mice were more cytotoxic against L929 cells than macrophages from lethal infections [104]. Stevenson and colleagues showed that depletion of macrophages in mice treated with silica significantly impaired MYO10 their ability to control P. chabaudi parasites [105]. The susceptibility of A/J mice to P. chabaudi infection also correlated with impaired macrophage activation and effector functions, including impaired expression of MHC-II, decreased production of IL-12 p70 and decreased strength of the respiratory burst [106]. Monocytes and macrophages played a significant role in the control of the early parasitaemia of both lethal and nonlethal P. yoelii infections [107]. Mice given clodronate-encapsulated liposomes to deplete them of macrophages failed to control nonlethal P. yoelii infections, suggesting that a strong early innate response was needed to control infection (107).