Signaling between mammalian adiponectin and a mosquito adiponectin receptor reduces Plasmodium transmission.

IMPORTANCE: When a female mosquito takes a blood meal from a mammalian host, components of the blood meal can affect mosquito fitness and indirectly influence pathogen infectivity. We identified a pathway involving an Anopheles gambiae adiponectin receptor, which, triggered by adiponectin from an incoming blood meal, decreases Plasmodium infection in the mosquito. Activation of this pathway negatively regulates lipophorin expression, an important lipid transporter that both enhances egg development and Plasmodium infection. This is an unrecognized cross-phyla interaction between a mosquito and its vertebrate host. These processes are critical to understanding the complex life cycle of mosquitoes and Plasmodium following a blood meal and may be applicable to other hematophagous arthropods and vector-borne infectious agents.

A mosquito AgTRIO mRNA vaccine contributes to immunity against malaria.

Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the skin of a vertebrate host. To prevent malaria, vaccination is the most effective strategy and there is an urgent need for new strategies to enhance current pathogen-based vaccines. Active or passive immunization against a mosquito saliva protein, AgTRIO, contributes to protection against Plasmodium infection of mice. In this study, we generated an AgTRIO mRNA-lipid nanoparticle (LNP) and assessed its potential usefulness as a vaccine against malaria. Immunization of mice with an AgTRIO mRNA-LNP generated a robust humoral response, including AgTRIO IgG2a isotype antibodies that have been associated with protection. AgTRIO mRNA-LNP immunized mice exposed to Plasmodium berghei-infected mosquitoes had markedly reduced initial Plasmodium hepatic infection levels and increased survival compared to control mice. In addition, as the humoral response to AgTRIO waned over 6 months, additional mosquito bites boosted the AgTRIO IgG titers, including IgG1 and IgG2a isotypes, which offers a unique advantage compared to pathogen-based vaccines. These data will aid in the generation of future malaria vaccines that may include both pathogen and vector antigens.

Grappling with the tick microbiome.

Ixodes scapularis and Ixodes pacificus are the predominant vectors of multiple human pathogens, including Borrelia burgdorferi, one of the causative agents of Lyme disease in North America. Differences in the habitats and host preferences of these closely related tick species present an opportunity to examine key aspects of the tick microbiome. While advances in sequencing technologies have accelerated a descriptive understanding of the tick microbiome, molecular and mechanistic insights into the tick microbiome are only beginning to emerge. Progress is stymied by technical difficulties in manipulating the microbiome and by biological variables related to the life cycle of Ixodid ticks. This review highlights these challenges and examines avenues to understand the significance of the tick microbiome in tick biology.