Malaria sporozoite: migrating for a living – a response

Abstract

In a recent paper, Carrolo et al. reported experiments performed using Plasmodium yoelii and Hepa 1–6 cells showing that cells wounded mechanically or by migrating sporozoites release an infection susceptibility inducing factor (ISIF) into the medium, which enhances infection [1xHepatocyte growth factor and its receptor are required for malaria infection. Carrolo, M. et al. Nat. Med. 2003; 9: 1363–1369Crossref | PubMed | Scopus (84)See all References][1]. Using Plasmodium berghei sporozoites, the authors then identified HGF as the ISIF, based on the observation that addition of HGF to the cultures has the same effects on infection as conditioned-medium ISIF, and, more importantly, that ISIF activity is neutralized by anti-HGF antibodies. Mota argues that it is difficult to envisage that, although P. yoelii and P. berghei infections can be increased by the same factor, and that primary hepatocytes produce this factor and respond to it, the system will be different with respect to this factor between the two species.However, we consider that it is too premature to conclude that HGF/Met signalling is a general feature of Plasmodium sporozoite infection for three reasons. First, P. yoelii and P. berghei display major differences with regard to sporozoite infection, including a differential CD81 requirement and a better infectivity for mice by P. yoelii. Therefore, interpreting results from one species to the other requires great caution. Second, although both recombinant HGF and conditioned culture medium were shown to have similar effects on P. berghei infection, one can hardly conclude whether HGF mediates all ISIF activity, or if other factors in the conditioned medium also account for the ISIF activity. In the absence of experimental confirmation that HGF has an ISIF activity on P. yoelii, we think it is too early to ascertain that the same factor mediates ISIF activity for both species. Finally, Mota and colleagues found that HGF/Met signalling induces a host cytoskeleton remodelling that is required for P. berghei infection, based on the observation that cytochalasin D inhibits early steps of the parasite development. Our observation that cytochalasin D does not inhibit P. yoelii development clearly indicates that the system is different between the two species, at least in the mechanisms involved (Silvie et al., unpublished results). Interestingly, Mota reports a background activation of Met in Hepa 1–6 cells. In this regard, it can be expected that interfering with Met signalling probably has detrimental effects on survival and proliferation of hepatoma cells, thus supporting our hypothesis that the role of HGF/Met signalling during Plasmodium infection might be to promote the survival of infected cells.