Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells

In order to gain a better understanding of gene expression during early malaria infection, we conducted microarray analysis of early blood responses in mice infected with erythrocytic stage Plasmodium chabaudi. Immediately following infection, we observed coordinated and sequential waves of immune responses, with interferon-associated gene transcripts dominating by 16 hours post-infection, followed by strong increases in natural killer (NK) cell-associated and MHC class I-related transcripts by 32 hours post-infection. We hypothesized that the observed elevation in NK cell-associated transcripts could be the result of a dramatic increase in the proportion of NK cells in the blood during infection, which we confirmed by flow cytometry. Subsequent microarray analysis of NK cells isolated from the peripheral blood of infected mice revealed a cell proliferation expression signature consistent with the observation that NK cells replicate in response to infection. Early proliferation of NK cells was directly observed in studies with adoptively transferred cells in infected mice. These data indicate that the early response to P. chabaudi infection of the blood is marked by a primary wave of interferon with a subsequent response by NK cells. Keywords: murine whole blood response to Plasmodium chabaudi infection We analyzed a series of 36 MEEBO arrays on which were hybed RNA amplified from whole blood of C57BL/6 mice either mock-infected or infected with P. chabaudi AS.