Diseases transmitted by insects (vector borne) account for over 17% of the infectious disease burden globally. Most of these diseases lack efficient mammalian vaccines or treatments, and thus heavily rely on vector control to prevent or reduce transmission. Anopheles and tsetse fly are the two vectors involved in malaria and sleeping sickness transmission, respectively. Current vector control methods largely involve the use of insecticides that are environmentally undesirable, and have diminishing efficacy in light of the emergence of insecticide resistance observed in insects. Understanding the mechanisms that influence vector-parasite transmission biology can help develop new control methods. There is growing evidence that the capacity to transmit parasites (vector competence) is influenced by vector innate immune responses and associations with native microbes. The two disease vectors, mosquitoes and tsetse flies, have varying life histories and different associations with gut microbiota. An important component of the innate immune response to pathogens involves Peptidoglycan Recognition Proteins, PGRPs, which recognize pathogen specific molecules and regulate host immune responses that ultimately clear pathogens. We have identified that the PGRP repertoire and functions in tsetse and mosquito vary in accordance with their different life histories and symbiotic associations. We also found that native microbiota influence vector competence through essential roles they play in host immunity and metabolism. This proposal builds on our preliminary studies and expands our previous findings to: 1) characterize and compare PGRP functions that differ in Anopheles and tsetse focusing on PGRP-LB and PGRP-LD and 2) investigate immune and metabolic contribution of the gut microbiota to vector competence. Implementation of our goals will expand our knowledge on 1) the structure and regulation of PGRPs contributing to vector competence, and 2) influence of metabolic interactions between vectors and microbiota on disease transmission traits. These findings have the potential to advance knowledge on tripartite interactions between vectors, symbionts and parasites, and to develop novel targets for disrupting pathogen transmission.

Public Health Relevance

Anopheles mosquito and tsetse fly are important disease vectors that transmit malaria and African trypanosomiasis, for which there are limiting control tools. Both vectors display natural resistance to parasite transmission, and rely on their innate immune system to eliminate pathogens in the gut during the early phase of infection, but each vector has different associations with environmental and symbiotic microbiota that influence their immune responses. Here we will focus and compare the two influential factors that shape vector competence: the varying roles of the peptidoglycan recognition proteins in the two disease vectors, and the role(s) of microbiota on host metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI129819-03
Application #
9664580
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2017-04-12
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Fudan University
Department
Type
DUNS #
420045148
City
Shanghai
State
Country
China
Zip Code
200433
Wang, Mengfei; Zhu, Dan; Dai, Jianfeng et al. (2018) Tissue Localization and Variation of Major Symbionts in Haemaphysalis longicornis, Rhipicephalus haemaphysaloides, and Dermacentor silvarum in China. Appl Environ Microbiol 84:
Song, Xiumei; Wang, Mengfei; Dong, Li et al. (2018) PGRP-LD mediates A. stephensi vector competency by regulating homeostasis of microbiota-induced peritrophic matrix synthesis. PLoS Pathog 14:e1006899
Wang, Jingwen; Song, Xiumei; Wang, Mengfei (2018) Peptidoglycan recognition proteins in hematophagous arthropods. Dev Comp Immunol 83:89-95