Malaria continues to be a global health problem where the mosquito Anopheles gambiae s.s. serves as a major vector for Plasmodium falciparum. Studying mosquito immunity is of grave importance because knowledge gained from these studies can be applied to future methods of abolishing the disease transmission cycle of malaria. One main aspect of mosquito immunity is the cellular response provided by hemocytes. Relevance of their importance comes from reports of TEP-1 and LRIM1, which are (1) produced solely in hemocytes and (2) are vital for malaria parasite clearance. This proposal will study molecular mechanisms behind regulating mosquito hemocyte homeostasis after a blood meal, and what affect this has on mosquito immunity to malaria parasites. The long-term goal is to understand the dynamics of cellular immunity in mosquitoes and its role in pathogen transmission.
The specific aims are (1) determine a molecular mechanism of hemocyte proliferation after a blood meal, (2) determine a molecular mechanism through which hemocytes are cleared after blood meal-induced hemocyte proliferation, and (3) determine what role hemocyte homeostasis has on immunity. To determine what regulates hemocyte homeostasis, reverse genetics of pathways of interest and quantitative assays measuring hemocyte abundance will be employed. To determine what role hemocyte homeostasis has on immunity, Plasmodium berghei infection intensities will be determined in reverse genetic backgrounds of altered signaling in hemocytes after blood meal. Upon completion of these research goals, the molecular mechanisms responsible for regulating hemocyte numbers after a blood meal will be determined and their consequences on mosquito immunity elucidated. Importantly, this study will establish novel methodologies and paradigms for cellular immunity in insects that are likely to be applicable to other vector-borne diseases. The health relevance of this proposal is the importance of hemocytes in malaria parasite clearance, and the obvious benefits the mosquito has when the number of circulating hemocytes increases after blood meal.

Public Health Relevance

Malaria is a major global health problem where a major factor behind malaria transmission is Plasmodium infection of the mosquito Anopheles gambiae. A major component behind how the mosquito fights Plasmodium infection is the cellular immune response, hemocytes. Due to the obligation of A. gambiae to take a blood meal to complete its life cycle, this proposal aims to understand how a blood meal affects homeostasis of hemocytes and determine what effect this has on immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI104154-01A1
Application #
8594447
Study Section
Special Emphasis Panel (ZRG1-F13-C (20))
Program Officer
Costero, Adriana
Project Start
2013-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$55,670
Indirect Cost
Name
Kansas State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
929773554
City
Manhattan
State
KS
Country
United States
Zip Code
66506