This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01928-06v1 75/5/2523    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Donovan, M. J. Articles by McDowell, M. A. Search for Related Content PubMed PubMed Citation Articles by Donovan, M. J. Articles by McDowell, M. A.

Uninfected Mosquito Bites Confer Protection against Infection with Malaria Parasites

Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556,¹ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892²

Received 6 December 2006/ Returned for modification 14 January 2007/ Accepted 17 February 2007

Despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. New insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease (A. Bjorkman and A. Bhattarai, Acta Trop. 94:163-169, 2005); ultimately successful vaccine strategies will undoubtedly be multifactorial, incorporating multiple antigens and targeting diverse aspects of the malaria parasites’ biology (M. F. Good et al., Immunol. Rev. 201:254-267, 2004). Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to Plasmodium yoelii infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquito-transmitted pathogens.

Published ahead of print on 5 March 2007.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Gomes, R., Teixeira, C., Teixeira, M. J., Oliveira, F., Menezes, M. J., Silva, C., de Oliveira, C. I., Miranda, J. C., Elnaiem, D.-E., Kamhawi, S., Valenzuela, J. G., Brodskyn, C. I. (2008). Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proc. Natl. Acad. Sci. USA 105: 7845-7850 [Abstract] [Full Text]