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

Study: Molecular mechanisms of insect immune memory and pathogen transmission. Image Credit: nobeastsofierce/Shutterstock

Background

Dengue, malaria, filariasis, and Zika are among the predominant insect-borne infectious diseases on the earth. Over the previous couple of a long time, dengue and malaria have increased significantly. Moreover, although insecticides reduce the spread of insect-borne diseases in some regions of the world, increasing resistance to insecticides in natural insect populations indicates the necessity for alternate strategies to limit the transmission of insect-borne diseases.

One in every of the areas gaining attention is immune priming to scale back the transmission of the disease. The competence of the vector, which is the flexibility of the vector to transmit the pathogen, is dependent upon its immune response. In insects, immunity is regulated by signaling pathways reminiscent of the c-Jun N-terminal kinase (JNK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), immune deficiency (IMD), Toll, and ribonucleic acid interference (RNAi) pathways. Recent research in vector-borne diseases has been focused on using these molecular mechanisms to focus on immune priming and reduce disease transmission.

Insect immune systems

Since insects depend on an innate immune system, the flexibility to develop and sustain an adaptive immune response from exposure to pathogens was considered lacking. Nevertheless, studies have provided evidence of immune priming in insects, where exposure to pathogens brings a couple of sustained change in cells that enhances the immune response during subsequent infections.

In cockroaches (Periplaneta americana), immunization with inactivated Pseudomonas aeruginosa was shown to guard the insects against infections with the live bacteria, with the consequences lasting for weeks. Similar results were seen in Drosophila immunized with Streptococcus pneumoniae. Studies show that immune priming may or is probably not 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 effects lasted only three days. Nevertheless, priming in insect larvae was shown to extend immunity within the adult form.

Other aspects, reminiscent of stress from lack of nutrition, competition, and injury, were also shown to provide phenotypes much like priming. While evidence suggests that immune priming is analogous to immune memory, the pathways and molecular mechanisms remain largely unexplored.

Evidence of immune priming

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

Female fruit flies exposed to positive single-stranded RNA viruses showed transgenerational immune priming (TGIP) with sequence-specific and RNA-dependent antiviral immunity displayed within the offspring for the subsequent five generations. Similar TGIP was exhibited in Aedes aegypti mosquito larvae when the adult females were exposed to the chikungunya virus. Although viral DNA is believed to play a vital role in TGIP, the mechanisms of transfer and amplification of viral DNA remain unclear.

Anopheles mosquitoes have shown hemocyte-dependent enhanced immunity against subsequent infections after exposure to Plasmodium. Studies have reported the role of gut microbiota in establishing and recalling antiplasmodial immune memory, which is everlasting and is dependent upon circulating granulocytes. Eicosanoid lipids reminiscent of lipoxins and prostaglandins play the role of signaling molecules within the coordinated immunity seen in various insect tissues.

Heme-peroxidases HPX7 and HPX8, induced during Plasmodium infection, mediate the synthesis of prostaglandin E2 (PGE2) through midgut microbiota. The discharge of PGE2 triggers the discharge of the hemocyte differentiation factor, which is a lipoxin-lipocalin complex. PGE2 also elicits double-peroxidase increases by fat body cells often known as oenocytes.

Trained immunity

Recent research has focused on immune training, wherein the transcription levels of immune effectors return to the basal state after the initial exposure to the pathogen. The next infection leads to a greater response from effector cells than within the case of immune priming. Immune training is non-specific, with exposure to fungal pathogens protecting the insects against bacterial infection. Immune training is believed to rely upon energy metabolism shifts and the involvement of the goal of the rapamycin-hypoxia-inducible factor 1-alpha (TOR-HIF1α) pathway.

Conclusions

Overall, the review suggested that although insect immunity is very adaptable, it only limits the infection and doesn’t eliminate it. Nevertheless, modulation of innate immunity in insects through immune priming and training are potentially essential strategies to scale back the transmission of insect-borne diseases. The role of regulatory signaling pathways and modulation of immunity through epigenetic modifications must be explored further.