Modulation of insect immunity to regulate vector-borne illnesses

Modulation of insect immunity to control vector-borne diseases

A recent review article published in PLOS Pathogens discussed current research on the role of molecular mechanisms in mediating immune priming in insects and regulating transmission of vector-borne diseases.

Study: Molecular Mechanisms of Insect Immune Memory and Transmission of Pathogens. Credit: nobeastsofierce/Shutterstock


Dengue, malaria, filariasis and Zika are among the most prevalent insect-borne infectious diseases worldwide. Dengue and malaria have increased significantly in recent decades. Although insecticides are reducing the spread of insect-borne diseases in some regions of the world, increasing resistance to insecticides in natural insect populations points to the need for alternative strategies to limit the transmission of insect-borne diseases.

One of the areas drawing attention is immune priming to reduce transmission of the disease. The competence of the vector, i.e. the ability of the vector to transmit the pathogen, depends on its immune response. In insects, immunity is regulated by signaling pathways such as N-terminal c-Jun kinase (JNK), Janus kinase signal transducer and activator of transcription (JAK-STAT), immunodeficiency (IMD), Toll, and ribonucleic acid interference ( RNAi) pathways. Recent research on vector-borne diseases has focused on harnessing these molecular mechanisms to stimulate the immune system and reduce disease transmission.

immune system of insects

Because insects rely on an innate immune system, it has been hypothesized that they lack the ability to develop and maintain an adaptive immune response to exposure to pathogens. However, studies have provided evidence of immune priming in insects, where exposure to pathogens causes a sustained change in cells that enhances the immune response during subsequent infections.

In cockroaches (Periplaneta americana), it was shown that immunization with inactivated Pseudomonas aeruginosa protected the insects from infection with the live bacteria for weeks. Similar results were observed in Drosophila immunized with Streptococcus pneumoniae. Studies show that immune priming may or may not be specific to the pathogen and may extend to other life stages of the insect. When P. americana immunized with P. aeruginosa was exposed to other bacteria, the protective effect lasted only three days. However, priming in insect larvae has been shown to increase immunity in the adult form.

Other factors, such as stress from malnutrition, competition, and injury, also resulted in priming-like phenotypes. While evidence suggests that immune priming is similar to immune memory, the signaling pathways and molecular mechanisms remain largely unexplored.

Evidence of immune priming

The antiviral immunity of adult Drosophila is enhanced when the hemocytes produce secondary viral small interfering RNA (siRNA) using viral deoxyribonucleic acid (DNA) as a template. The siRNA is delivered to other insect tissues through exosome-like vesicles. A study with Drosophila C virus showed that oral infection with the virus in fruit fly larvae increased tolerance to infection in adult forms.

Female fruit flies exposed to positive single-stranded RNA viruses demonstrated transgenerational immune priming (TGIP) with sequence-specific and RNA-dependent antiviral immunity demonstrated in the offspring for the next five generations. Similar TGIP was detected in Aedes aegypti mosquito larvae when the adult females were exposed to Chikungunya virus. Although viral DNA is believed to play an important role in TGIP, the mechanisms of viral DNA delivery and amplification remain unclear.

Anopheles mosquitoes have demonstrated hemocyte-dependent enhanced immunity against subsequent infection after exposure to Plasmodium. Studies have reported the role of the gut microbiota in the establishment and retrieval of antiplasmodial immune memory, which is persistent and dependent on circulating granulocytes. Eicosanoid lipids such as lipoxins and prostaglandins play the role of signaling molecules in coordinated immunity observed in various insect tissues.

The heme peroxidases HPX7 and HPX8, induced during Plasmodium infection, mediate the synthesis of prostaglandin E2 (PGE2) by the midgut microbiota. The release of PGE2 triggers the release of hemocyte differentiation factor, which is a lipoxin-lipocalin complex. PGE2 also triggers an increase in double peroxidase by fat body cells known as oenocytes.

Trained immunity

Recent research has focused on immune training, in which transcription levels of immune effectors return to baseline after initial exposure to the pathogen. Subsequent infection results in a better effector cell response than in immune priming. Immune training is non-specific as exposure to fungal pathogens protects the insects from bacterial infection. Immune training is thought to depend on changes in energy metabolism and involvement of the target of rapamycin hypoxia-inducible factor 1-alpha (TOR-HIF1α) signaling.


Overall, the review suggested that while insect immunity is highly adaptive, it only limits, rather than eliminates, infection. However, modulation of innate immunity in insects through immune priming and training are potentially important strategies to reduce transmission of insect-borne diseases. The role of regulatory signaling pathways and the modulation of immunity by epigenetic modifications needs to be further explored.