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Infection and Immunity, December 2008, p. 5873-5882, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00640-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Experimental Malaria Infection Triggers Early Expansion of Natural Killer Cells{triangledown} ,{dagger}

Charles C. Kim,1 Sunil Parikh,2 Joseph C. Sun,3,5 Alissa Myrick,4 Lewis L. Lanier,3,5 Philip J. Rosenthal,2 and Joseph L. DeRisi1,6*

Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California,1 Department of Medicine, University of California San Francisco, San Francisco, California,2 Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, California,3 Biology Scholars Program, University of California Berkeley, Berkeley, California,4 Cancer Research Institute, University of California San Francisco, San Francisco, California,5 Howard Hughes Medical Institute, Chevy Chase, Maryland6

Received 23 May 2008/ Returned for modification 13 July 2008/ Accepted 24 September 2008

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 h postinfection, followed by strong increases in natural killer (NK) cell-associated and major histocompatibility complex class I-related transcripts by 32 h postinfection. We showed by flow cytometry that the observed elevation in NK cell-associated transcripts was the result of a dramatic increase in the proportion of NK cells in the blood during infection. 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.


* Corresponding author. Mailing address: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA. Phone: (415) 476-4132. Fax: (415) 476-0806. E-mail: joe{at}derisilab.ucsf.edu

{triangledown} Published ahead of print on 29 September 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.


Infection and Immunity, December 2008, p. 5873-5882, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00640-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.