Novel systems to study vector-pathogen interactions in malaria

Abstract

Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating “de novo” genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.

One Health Perspective of Malaria Transmission

“…Transgenic mosquitoes could be a successful choice for developing a range of effective disease-fighting strategies as a result of the advancements made in genetic modification in recent years [109][110][111]. Arthropod control by genetic modification is an old concept that was independently researched in the 1930s, 1940s and 1950s by three pioneers: A. S. Serebrovskii (1940), F. L. Vanderplank (1947) and E. F. Knipling (1955) [112,113].…”

“…Arthropod control by genetic modification is an old concept that was independently researched in the 1930s, 1940s and 1950s by three pioneers: A. S. Serebrovskii (1940), F. L. Vanderplank (1947) and E. F. Knipling (1955) [112,113]. Furthermore, the 1970s saw a particular focus on studies concerning sterile males [109,110,114], which in turn prompted re-evaluation of the original concepts [109][110][111][115][116][117][118].…”

Immune Reactions of Vector Insects to Parasites and Pathogens

“…There are a large number of reviews in the last 10 years related to insect vector immunity including e.g., [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Most of these deal with a single group, genus or species of vector insects or even just with one key aspect of immunity such as the antimicrobial peptides (AMPs), signal molecules or infections caused by one particular parasite or pathogen.…”