DESCRIPTION (provided by applicant): There is considerable interest in understanding the mechanisms and function of mosquito innate immunity, with recent research in this area identifying important immune genes and metabolic pathways that appear to influence the ability of mosquitoes to transmit malaria. However nearly all such studies have been conducted under highly controlled lab environments, which is not what mosquitoes and Plasmodium parasites experience in the field. Natural malaria transmission occurs across a temperature range of 15-35 0 C, with the potential for considerable variation in conditions across temporal and spatial scales. We wish to test the hypothesis that temperature has significant impacts on mosquito immune function and vector competence, and to explore whether the insights gained under one set of controlled conditions are sufficient to understand variation in mosquito resistance/refractoriness in nature. We argue that mosquito immune function should be affected by environmental temperature because mosquitoes are small-bodied and cold-blooded. In other insect-parasite systems temperature has profound effects on parasite development and overall host resistance. Whether such effects occur with mosquitoes and malaria and if so, whether these effects are due to impacts of temperature on the parasite, on host immunity, or some combination of both, remains unclear. If temperature does affect mosquito immune function, then temperature may be a potent environmental parameter describing variation in mosquito resistance / refractoriness in natural vector populations and might also explain the disparities in immune responses to different Plasmodium parasites (in particular between some rodent malaria parasites and P. falciparum). More fundamentally, if mosquito immune response exhibits thermal sensitivity, the current approach of outlining immunological mechanism under standard lab conditions is insufficient for understanding natural or transgenic vector competence. PUBLIC HEALTH RELEVANCE: Current understanding of mosquito innate immunity derives almost exclusively from studies conducted under standard laboratory conditions. Yet in nature, mosquitoes and parasites interact across a range of environments. We wish to test the hypothesis that environmental temperature significantly shapes mosquito immune function and determine whether notional resistance mechanisms revealed in the lab can explain variation in mosquito resistance to malaria in the field.
|Effective start/end date||6/1/11 → 5/31/14|
- National Institutes of Health: $147,400.00
- National Institutes of Health: $257,950.00
Metabolic Networks and Pathways