Host-pathogen interaction in arthropod vectors: Lessons from viral infections

Abstract

Haematophagous arthropods can harbor various pathogens including viruses, bacteria, protozoa, and nematodes. Insects possess an innate immune system comprising of both cellular and humoral components to fight against various infections. Haemocytes, the cellular components of haemolymph, are central to the insect immune system as their primary functions include phagocytosis, encapsulation, coagulation, detoxification, and storage and distribution of nutritive materials. Plasmatocytes and granulocytes are also involved in cellular defense responses. Blood-feeding arthropods, such as mosquitoes and ticks, can harbour a variety of viral pathogens that can cause infectious diseases in both human and animal hosts. Therefore, it is imperative to study the virus-vector-host relationships since arthropod vectors are important constituents of the ecosystem. Regardless of the complex immune response of these arthropod vectors, the viruses usually manage to survive and are transmitted to the eventual host. A multidisciplinary approach utilizing novel and strategic interventions is required to control ectoparasite infestations and block vector-borne transmission of viral pathogens to humans and animals. In this review, we discuss the arthropod immune response to viral infections with a primary focus on the innate immune responses of ticks and mosquitoes. We aim to summarize critically the vector immune system and their infection transmission strategies to mammalian hosts to foster debate that could help in developing new therapeutic strategies to protect human and animal hosts against arthropod-borne viral infections.

Keywords: antiviral defense; haemocoel; haemocytes; immune system; innate immunity; virus circulation.

Figure 1

Insect innate immune mechanisms: When the insect’s immune system recognizes pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs), pathogens encounter a complex system of humoral and cellular responses. Humoral responses include the production of antimicrobial peptides (AMPs), reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI), and a complex enzymatic cascade to regulate clotting or melanization. Cellular immune response involves various haemocytes that participate in phagocytosis/nodulation/encapsulation for pathogen clearance from haemolymph. In addition, different immune cells release toxic factors to kill pathogens, i.e. cell-mediated killing (complement components, etc.). These events take place in the haemocoel of the ticks. The series of immune reactions depict innate immunity. Clotting protein is a unique lipoprotein. Hemolymph clotting is induced upon transglutaminase (TGase) release from hemocytes/tissues. Calcium ions play an important role in the cascade leading to coagulation. TGase is involved in the coagulation, disturbing the chemical nature of the target pathogens. Peroxinectin is an opsonin that does attachment, spreads, and induces degranulation. SOD produces H₂O₂ from which hypohalic acid is released, which is a toxic substance, Prophenoloxidase activating system (proPO system) is an efficient part of the innate immune response. bGBP is a pattern recognition protein known to bind β-1,3, glucan. Masquerade (Mas-) like protein is also a multifunctional innate immune protein, an opsonin-like peroxinectin, capable of doing pathogen binding, inducing degranulation, and pathogen clearance. TGase, transglutaminase; Ca²⁺, Calcium, SOD, superoxide dismutase; βGBP, glucan with β-1,3 glucan binding protein; Mas-like protein,-- Masquerade- like protein.

Figure 2

Mosquitoes transmit viruses (Zika, yellow fever, chikungunya, dengue, and West Nile), nematodes (filariasis), and Plasmodium parasites (malaria) in humans.

Figure 3

Ingestion, replication, and dissemination of virus in the mosquito, (A) mosquito ingests the blood of infected host, (B) ingested virus infects the midgut (C) after replication in the midgut virus spreads in the haemocoel, (D) after dissemination virus infects salivary glands (E) finally mosquito transmits virus to host by biting it.

Figure 4

Acquisition, development, and transmission of pathogens by ticks. 1. When ticks bite, pathogens are ingested with the meal. 2. Pathogens either stay until the next meal or move through the gastrointestinal epithelium 3. The extraneous pathogen can potentially harm the tick’s body, depending on the type of pathogen. 4. Pathogens enter the salivary gland and attack the acini through the epithelium. 5,6. Pathogens, along with saliva, are introduced into a new host during feeding, disrupting host homeostasis and setting off inflammatory responses.