Mosquito-borne viral diseases are a major concern of global health and result in significant economic losses in many countries. As natural vectors, mosquitoes are very permissive to and allow systemic and persistent arbovirus infection. Intriguingly, persistent viral propagation in mosquito tissues neither results in dramatic pathological sequelae nor impairs the vectorial behavior or lifespan, indicating that mosquitoes have evolved mechanisms to tolerate persistent infection and developed efficient antiviral strategies to restrict viral replication to non-pathogenic levels. Here, we provide an overview of recent progress in understanding mosquito antiviral immunity and advances in the strategies by which mosquitoes control viral infection in specific tissues.
The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.
C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden.
The long-term evolutionary interaction between the host immune system and symbiotic bacteria determines their cooperative rather than antagonistic relationship. It is known that commensal bacteria have evolved a number of mechanisms to manipulate the mammalian host immune system and maintain homeostasis. However, the strategies employed by the microbiome to overcome host immune responses in invertebrates still remain to be understood. Here, we report that the gut microbiome in mosquitoes utilizes C-type lectins (mosGCTLs) to evade the bactericidal capacity of antimicrobial peptides (AMPs). Aedes aegypti mosGCTLs facilitate colonization by multiple bacterial strains. Furthermore, maintenance of the gut microbial flora relies on the expression of mosGCTLs in A. aegypti. Silencing the orthologues of mosGCTL in another major mosquito vector (Culex pipiens pallens) also impairs the survival of gut commensal bacteria. The gut microbiome stimulates the expression of mosGCTLs, which coat the bacterial surface and counteract AMP activity. Our study describes a mechanism by which the insect symbiotic microbiome offsets gut immunity to achieve homeostasis.
SummaryThe metazoan gut harbors complex communities of commensal and symbiotic bacterial microbes. The quantity and quality of these microbes fluctuate dynamically in response to physiological changes. The mechanisms that hosts developed to respond to and manage such dynamic changes and maintain homeostasis remain largely unknown. Here, we identify a dual oxidase (Duox)-regulating pathway that contributes in maintaining homeostasis in the gut of both Aedes aegypti and Drosophila melanogaster. We show that a gut membrane-associated protein, named Mesh, plays an important role in controlling proliferation of gut bacteria by regulating Duox expression through an Arrestin-mediated MAPK JNK/ERK phosphorylation cascade. Expression of both Mesh and Duox is correlated with the gut bacterial microbiome that, in mosquitoes, increases dramatically soon after a blood meal. Ablation of Mesh abolishes Duox induction leading to an increase of the gut microbiome load. Our study reveals that the Mesh-mediated signaling pathway is a central homeostatic mechanism of the insect gut.
Antimicrobial peptides (AMPs) are an important group of immune effectors that play a role in combating microbial infections in invertebrates. Most of the current information on the regulation of insect AMPs in microbial infection have been gained from Drosophila, and their regulation in other insects are still not completely understood. Here, we generated an AMP induction profile in response to infections with some Gram-negative, -positive bacteria, and fungi in Aedes aegypti embryonic Aag2 cells. Most of the AMP inductions caused by the gram-negative bacteria was controlled by the Immune deficiency (Imd) pathway; nonetheless, Gambicin, an AMP gene discovered only in mosquitoes, was combinatorially regulated by the Imd, Toll and JAK-STAT pathways in the Aag2 cells. Gambicin promoter analyses including specific sequence motif deletions implicated these three pathways in Gambicin activity, as shown by a luciferase assay. Moreover, the recognition between Rel1 (refer to Dif/Dorsal in Drosophila) and STAT and their regulatory sites at the Gambicin promoter site was validated by a super-shift electrophoretic mobility shift assay (EMSA). Our study provides information that increases our understanding of the regulation of AMPs in response to microbial infections in mosquitoes. And it is a new finding that the A. aegypti AMPs are mainly regulated Imd pathway only, which is quite different from the previous understanding obtained from Drosophila.
In this study, C3N4@Ag-Bi2WO6 with flower-like architecture was successfully prepared through a facile process. The C3N4@Ag-Bi2WO6 particles with 2–4 μm diameters present remarkable enhanced visible light absorption and electron–hole separation efficiency. Compared with Bi2WO6, Ag-Bi2WO6, and C3N4@Bi2WO6 systems, the C3N4@Ag-Bi2WO6 system exhibits optimal photocatalytic activities in both the degradation of RhB and hydrogen production out of water under visible light irradiation. We propose that these results are attributed to the synergy effects of Ag, g-C3N4, and Bi2WO6 nanophase structures in the C3N4@Ag-Bi2WO6 composites, which results in a fast electron–hole separation and slow charge recombination by a Z-scheme mechanism and ultimately in a higher photocatalytic activity.
Core Ideas SOC and AOC were higher in CT and RT treatments than RTO at 0 to 5, 5 to 10, and 10 to 20 cm. Lability, LI, and CMI in the CT treatment were higher than NT treatment at 0 to 5 and 10 to 20 cm. SOC stocks were significantly higher in NT at 0 to 5 cm than under the RTO treatment. SOC stocks were significantly higher in CT and RT at 5 to 10 and 10 to 20 cm than under RTO. Interactions between tillage and soil organic carbon (SOC) impact soil structure, soil quality, and the calculated soil carbon management index (CMI). However, the effects of different tillage and residue management systems on the dynamics of SOC remain unclear under double‐cropping rice (Oryza sativa L.). Therefore, the effects of soil tillage and incorporated residues on soil bulk density, SOC, soil active organic carbon (AOC), and the CMI were studied in a southern China double‐cropped rice system. The experiment included four tillage treatments: conventional tillage with residue incorporation (CT), rotary tillage with residue incorporation (RT), no tillage with residue retention (NT), and rotary tillage with residue removed as a control (RTO). The results indicated that soil bulk density increased under NT in the 0‐ to 20‐cm layer, SOC was higher under NT than that of other treatments, and SOC in the 5‐ to 20‐cm layer was higher under CT and RT than under NT and RTO. The greatest SOC and AOC contents were observed under CT at the 5‐ to 10‐cm and 10‐ to 20‐cm layers. The CMI was used to assess the soil quality change with different soil tillage practices. The application of residue combined with conventional tillage or rotary tillage was more effective for increasing soil carbon pool index (CPI) and CMI than was rotary tillage with the residue was removed. The CMI for the 0‐ to 10‐cm depth under RT and CT were higher (P < 0.05) than the NT treatment. Meanwhile, RT significantly enhanced the SOC stocks over the RTO treatment at three different depths. As a result, based on soil CMI and C storage, double‐cropping rice using a no‐tillage system where crop residues are not removed could increase SOC in the surface 5 cm.
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