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Ticks, triatomines, mosquitoes and sand flies comprise a large number of haematophagous arthropods considered vectors of human infectious diseases. While consuming blood to obtain the nutrients necessary to carry on life functions, these insects can transmit pathogenic microorganisms to the vertebrate host. Among the molecules related to the blood-...
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... molecular patterns (PAMPs), resulting in antimicrobial peptides synthesis, enzymatic cascades that can induce coagulation of haemolymph, wound healing and melanin formation. In addition, it may also activate phagocytosis, encapsulation, nodulation and antiviral response. Our current view of the arthropods immune system is represented in Fig. 3. Three major arthropod signalling immune pathways involved in the humoral and cellular responses have been described: the Toll, the immunodeficiency (IMD), and the JAK-STAT [51]. Innate immune response is triggered upon activation of Toll and IMD pathways, inducing antimicrobial peptide gene expression [52]. The JAK-STAT pathway also ...
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... These cysteine peptidases may complement the action of serine proteases in luminal protein digestion. Furthermore, the isoforms of cathepsin B and cathepsin L secreted in the PMG of this mosquito have been shown to play a role in digestion and immune response in triatomines, hemipterans and cyclorrhaphous Diptera [57,58]. The detection of these proteases suggests that the posterior segment of the midgut exhibits an acidic environment, given that cysteine proteases are most effective in an acidic pH [59]. ...
Toxorhynchites mosquitoes have an exclusively phytophagous feeding habit as adults, which leads to significant differences in their morphophysiology compared with hematophagous mosquitoes. However, the molecular mechanisms of digestion in this mosquito are not well understood. In this study, RNA sequencing of the posterior midgut (PMG) of the mosquito Toxorhynchites theobaldi was undertaken, highlighting its significance in mosquito digestion. Subsequently, a comparison was made between the differential gene expression of the PMG and that of the anterior midgut. It was found that the most abundant proteases in the PMG were trypsin and chymotrypsin, and the level of gene expression for enzymes essential for digestion (such as serine protease, α-amylase and pancreatic triacylglycerol lipase) and innate immune response (including catalase, cecropin-A2 and superoxide dismutase) was like that of hematophagous mosquitoes. Peritrophin-1 was detected in the entire midgut, with an elevated expression level in the PMG. Based on our findings, it is hypothesized that a nonhematophagic habit might have been exhibited by the ancestor of T. theobaldi, and this trait may have been retained. This study represents a pioneering investigation at the molecular level of midgut contents in a nonhematophagous mosquito. The findings offer valuable insights into the evolutionary aspects of feeding habits in culicids.
... The ability of hematophagous arthropods to spread various infectious agents, or vector-borne pathogens (VBPs) between a wide range of organisms ultimately leads to the occurrence of vector-borne diseases (VBDs) [1]. Important arthropod vectors of infectious diseases include ticks (Ixodoidea), mosquitoes (Culicidae), sandflies (Phlebotominae), tsetse flies (Glossinidae), black flies (Simuliidae), and kissing bugs (Triatominae). ...
Vector-borne pathogens (VBPs) causing vector-borne diseases (VBDs) can circulate among humans, domestic animals, and wildlife, with cattle in particular serving as an important source of exposure risk to humans. The close associations between humans and cattle can facilitate the transmission of numerous VBPs, impacting public health and economic security. Published studies demonstrate that cattle can influence human exposure risk positively, negatively, or have no effect. There is a critical need to synthesize the information in the scientific literature on this subject, in order to illuminate the various ecological mechanisms that can affect VBP exposure risk in humans. Therefore, the aim of this systematic review was to review the scientific literature, provide a synthesis of the possible effects of cattle on VBP risk to humans, and propose future directions for research. This study was performed according to the PRISMA 2020 extension guidelines for systematic review. After screening 470 peer-reviewed articles published between 1999–2019 using the databases Web of Science Core Collection, PubMed Central, CABI Global Health, and Google Scholar, and utilizing forward and backward search techniques, we identified 127 papers that met inclusion criteria. Results of the systematic review indicate that cattle can be beneficial or harmful to human health with respect to VBDs depending on vector and pathogen ecology and livestock management practices. Cattle can increase risk of exposure to infections spread by tsetse flies and ticks, followed by sandflies and mosquitoes, through a variety of mechanisms. However, cattle can have a protective effect when the vector prefers to feed on cattle instead of humans and when chemical control measures (e.g., acaricides/insecticides), semio-chemicals, and other integrated vector control measures are utilized in the community. We highlight that further research is needed to determine ways in which these mechanisms may be exploited to reduce VBD risk in humans.
... Scientists worldwide have been making significant contributions to the field of parasitic infections transmitted by arthropod vectors investigating their molecular biology. Arthropod proteases play essential roles in their blood-feeding behavior, egg development, and immunity (Santiago et al., 2017). Proteases are multifunctional enzymes that hydrolyze one or more peptide bonds in a protein or peptide. ...
... Our previous review covered contemporary advances in the proteases from hematophagous arthropod vectors up to 2016 (Santiago et al., 2017). In this opinion article, we summarize further research findings on vector proteases and emphasize their biotechnological potential for the development of innovative protease-based drugs with broad clinical applications. ...
... During the digestion process of blood components in the gut of hematophagous organisms, proteases function within a network of multiple enzymes that break down hemoglobin. These multipeptidase repertoires are mainly composed of serine proteases in mosquitoes and cysteine and aspartic proteases in ticks and triatomines (Santiago et al., 2017). Trypanosoma cruzi, the causative agent of Chagas disease, proliferates and develops inside the intestines of triatomine vectors. ...
... These genes are known to be key mediators of protein catabolism. In fact, they are key enzymes involved in the processing of high protein substrates, such as blood meals in ticks and other blood feeding animals (Alim et al., 2009;Santiago et al., 2017). Cathepsins are also involved in lipid processing (Thibeaux et al., 2018). ...
We report preliminary evidence of a symbiotic parabasalian protist in the guts of Peruvian mimic poison frog (Ranitomeya imitator) tadpoles. This species has biparental care and egg-feeding of tadpoles, while the related R. variabilis consumes the ancestral detritus diet in their nursery pools. Each species’ diet was experimentally switched, in the field and lab. Analyses of gut gene expression revealed elevated expression of proteases in the R. imitator field egg-fed treatment. These digestive proteins came from parabasalians, a group of protists known to form symbiotic relationships with hosts that enhance digestion. Genes that code for these digestive proteins are not present in the R. imitator genome, and phylogenetic analyses indicate that these mRNA sequences are from parabasalians. Bar-coding analyses of the tadpole microbiomes further confirmed this discovery. Our findings indicate the presence of parabasalian symbiotes in the intestines of the R. imitator tadpoles, that may aid the tadpoles in protein/lipid digestion in the context of an egg diet. This may have enabled the exploitation of a key ecological niche, allowing R. imitator to expand into an area with ecologically similar species (e.g., R. variabilis and R. summersi). In turn, this may have enabled a Müllerian mimetic radiation, one of only a few examples of this phenomenon in vertebrates.
... PRRs bind to the PAMPs and initiate opsonization of pathogens. The activation of downstream signaling induced by PRRs leads to the synthesis and secretion of effector molecules, for example reactive oxygen species (ROS), antimicrobial peptides (AMPs), and components of the phenoloxidase cascade; these effector molecules restrict infections and clear the intruding pathogens (8,(18)(19)(20). Blood sucking insects such as mosquitoes acquire various pathogens during blood feeding and their midgut epithelial cells act as the first line of defense and produce ROS and several AMPs. ...
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.
... Considering the important function of aspartic protease genes in the reproduction of insects [19], we screened and identified 42 aspartic protease genes from our previous transcriptome data of A. suturalis and the gene with the highest expression level among sexually mature females was selected for further study. In our research, we examined the cloning, expression and characterization of the cDNA that encodes A. suturalis aspartic protease (AsAP) and assessed its in vivo biological function using the RNAi-mediated knockdown method. ...
... The amplified transcript contained a 1137 bp open reading frame and a 142 bp 3 untranslated region that had a 29 bp polyadenylation tail that began 13 bp downstream from the consensus AATAAA eukaryotic polyadenylation signal ( Figure 1A). The transcript was predicted to encode a 378 amino acid protein with a mass of 43.01 kDa and have the domain characteristics of eukaryotic aspartic proteases, including a signal peptide (amino acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and an Asp domain (amino acids 65-375) ( Figure 1B). The deduced protein also had three potential N-glycosylation sites: amino acids 27-29 (NRS), 107-109 (NQS) and 127-129 (NGS) ( Figure 1B). ...
... Acid hydrolases that are deposited in the ovaries during vitellogenesis have been implicated in the degradation of vitellin [19,36]. For instance, in both Rhodnius prolixus and R. microplus, aspartic endopeptidases have been shown to play a role in vitellin degradation during embryogenesis [37][38][39]. ...
Adelphocoris suturalis Jakovlev (Hemiptera: Miridae) is an omnivorous agricultural pest that has severe economic impacts on a diverse range of agricultural crops. Although the targeted disruption of reproductive development among insects has been proposed as a novel control strategy for pest species, the current understanding of the physiology and molecular mechanisms of A. suturalis reproduction is very limited. In this study, we isolated a putative A. suturalisaspartic protease (AsAP) gene that is highly expressed in the fat body and ovaries of sexually mature females. The double-stranded RNA (dsRNA)-mediated knockdown of AsAP suppressed ovarian development and negatively impacted female fertility, which suggested that it plays an essential role in A. suturalis reproduction. The results of this study could help to expand our understanding of A. suturalis reproductive development and have the potential to facilitate the development of effective strategies for the better control of this pest species.
... In triatomines, the anti-protease activity may take place in the extracellular space, namely in the salivary content or in the intracellular environment. Serine proteinase inhibitors are a frequent component of sialomes from blood-feeding arthropods, including triatomines (Tanaka-Azevedo et al., 2010;Santiago et al., 2017). Here, 69 transcripts coding for protease inhibitors were extracted, including Kazal-type, cystatin, serpin, pacifastin, mucin and Kunitz-type ( Table 3). ...
Triatomines have evolved salivary glands that produce versatile molecules with various biological functions, including those leading their interactions with vertebrate hosts’ hemostatic and immunological systems. Here, using high-throughput transcriptomics and proteomics, we report the first sialome study on the synanthropic triatomine Triatoma sordida. As a result, 57,645,372 reads were assembled into 26,670 coding sequences (CDS). From these, a total of 16,683 were successfully annotated. The sialotranscriptomic profile shows Lipocalin as the most abundant protein family within putative secreted transcripts. Trialysins and Kazal-type protease inhibitors have high transcript levels followed by ubiquitous protein families and enzyme classes. Interestingly, abundant trialysin and Kazal-type members are highlighted in this triatomine sialotranscriptome. Furthermore, we identified 132 proteins in T. sordida salivary gland soluble extract through LC-MS/MS spectrometry. Lipocalins, Hemiptera specific families, CRISP/Antigen-5 and Kazal-type protein inhibitors proteins were identified. Our study provides a comprehensive description of the transcript and protein compositions of the salivary glands of T. sordida. It significantly enhances the information in the Triatominae sialome databanks reported so far, improving the understanding of the vector’s biology, the hematophagous behaviour, and the Triatominae subfamily’s evolution.
... Entre ellas se han descrito, Catepsinas, tipo Cisteína y/o Aspartato proteasas, enzimas de la familia Catepsina B, Catepsina D y Catepsina L. En este grupo, se han descrito TBCATL-1 y TBCATL-2 de Triatoma brasiliensis, RpCat de R. prolixus y, CatL1 y CatB1 de T. infestans. Estas enzimas digestivas, están presentes en el proceso de la degradación de proteínas y actúan a pH 5, correspondiente a la escala de pH del tracto intestinal de estos insectos [47], [63], [64]. Sin embargo, después de la digestión se presenta una concentración elevada de grupo hemo libre que puede afectar de manera física la bicapa de fosfolípidos de las células presentes en el intestino de los triatominos a través de la producción de ROS [65]. ...
Chagas disease is a parasitic disease caused by Trypanosoma cruzi and is transmitted mainly by vectors of the subfamily Triatominae, which evolutionarily have been considered obligate hematophagous insects. However, other feeding behaviors have been reported in this group of vectors. Alternate feeding behaviors in triatomines could change the way these insects are reared in the laboratory and enhance the study of vectorial transmission of this disease. Therefore, the present study aimed to evaluate the effect of hematophagous feeding and the impact of other feeding behaviors on biological efficacy in triatomines. A systematic literature review was performed to select the studies that had information about hematophagous feeding and other feeding behaviors. First, information was collected in databases with a previously established search strategy; the information from the studies was analyzed and selected considering the evolutionary, physiological, survival and reproductive aspects. Finally, the relevant information was synthesized and the risks of bias of selected studies were evaluated. Results show that the triatomines successfully adapted to hematophagy and that other feeding behaviors improve nutritional states when access to a blood source is deficient. Therefore, it’s suggested to study in laboratory conditions mixed food sources that allow modifications in strictly haematophagous breeding and feeding conditions in the short and medium term.
... Two metalloproteases are expressed in the hemolymph of R. prolixus infected with Enterobacter cloacae [51] and Trypanosoma rangeli [52]. These proteases are expressed in the fat body and their release into the hemolymph upon infection suggests their role in R. prolixus defense against pathogens [53]. Although the function of these proteins in the midgut is unknown, a function similar to that of the saliva could be expected [48]. ...
Chagas disease is a vector-borne parasitic disease caused by the flagellated protozoan Trypanosoma cruzi and transmitted to humans by a large group of bloodsucking triatomine bugs. Triatomine insects, such as Rhodnius prolixus, ingest a huge amount of blood in a single meal. Their midgut represents an important interface for triatomine–trypanosome interactions. Furthermore, the development of parasites and their vectorial transmission are closely linked to the blood feeding and digestion; thus, an understanding of their physiology is essential for the development of new strategies to control triatomines. In this study, we used label-free quantitative proteomics to identify and analyze the early effect of blood feeding on protein expression in the midgut of Rhodnius prolixus. We both identified and quantified 124 proteins in the anterior midgut (AM) and 40 in the posterior midgut (PM), which vary significantly 6 h after feeding. The detailed analysis of these proteins revealed their predominant involvement in the primary function of hematophagy, including proteases, proteases inhibitors, amino acids metabolism, primary metabolites processing, and protein folding. Interestingly, our proteomics data show a potential role of the AM in protein digestion. Moreover, proteins related to detoxification processes and innate immunity, which are largely accepted to be triggered by blood ingestion, were mildly modulated. Surprisingly, one third of blood-regulated proteins in the AM have unknown function. This work contributes to the improvement of knowledge on the digestive physiology of triatomines in the early hours post-feeding. It provides key information for selecting new putative targets for the development of triatomine control tools and their potential role in the vector competence, which could be applied to other vector species.
... Strictly speaking, digestion starts with hydrolysis of food by a vast array of digestive enzymes secreted after a meal (proteinases, carbohydrases, and lipases) that, together with nutrient transporting proteins, are needed to process nutrients in the gut (Santiago et al., 2017). However, in the context of hematophagous insects, proteases have received far more attention because blood is composed mainly of proteins (90% of dry weight), leading those insects to translate an arsenal of proteases to support protein digestion (Lehane, 2005;Brackney et al., 2010;Henriques et al., 2017;Sterkel et al., 2017). ...
... However, in the context of hematophagous insects, proteases have received far more attention because blood is composed mainly of proteins (90% of dry weight), leading those insects to translate an arsenal of proteases to support protein digestion (Lehane, 2005;Brackney et al., 2010;Henriques et al., 2017;Sterkel et al., 2017). In most insects, proteolysis is based on trypsin and other serine proteases, in contrast to triatomines and ticks, where aspartic and cysteine proteases drive protein digestion (Sojka et al., 2008;Santiago et al., 2017;Henriques et al., 2021). Initially, protein degradation was described as accomplished by a few enzymes of each type, but genome sequencing in mosquitoes, triatomines, sandflies and ticks showed the existence of multiple copies of enzymes in all classes, revealing extensive gene duplications that probably occurred after the acquisition of the blood-feeding habit, suggesting the need for redundancy or some type of functional differentiation among enzymes of the same family (Sojka et al., 2008;Henriques et al., 2017;Santiago et al., 2017). ...
... In most insects, proteolysis is based on trypsin and other serine proteases, in contrast to triatomines and ticks, where aspartic and cysteine proteases drive protein digestion (Sojka et al., 2008;Santiago et al., 2017;Henriques et al., 2021). Initially, protein degradation was described as accomplished by a few enzymes of each type, but genome sequencing in mosquitoes, triatomines, sandflies and ticks showed the existence of multiple copies of enzymes in all classes, revealing extensive gene duplications that probably occurred after the acquisition of the blood-feeding habit, suggesting the need for redundancy or some type of functional differentiation among enzymes of the same family (Sojka et al., 2008;Henriques et al., 2017;Santiago et al., 2017). ...
Blood-feeding arthropods are considered an enormous public health threat. They are vectors of a plethora of infectious agents that cause potentially fatal diseases like Malaria, Dengue fever, Leishmaniasis, and Lyme disease. These vectors shine due to their own physiological idiosyncrasies, but one biological aspect brings them all together: the requirement of blood intake for development and reproduction. It is through blood-feeding that they acquire pathogens and during blood digestion that they summon a collection of multisystemic events critical for vector competence. The literature is focused on how classical immune pathways (Toll, IMD, and JAK/Stat) are elicited throughout the course of vector infection. Still, they are not the sole determinants of host permissiveness. The dramatic changes that are the hallmark of the insect physiology after a blood meal intake are the landscape where a successful infection takes place. Dominant processes that occur in response to a blood meal are not canonical immunological traits yet are critical in establishing vector competence. These include hormonal circuitries and reproductive physiology, midgut permeability barriers, midgut homeostasis, energy metabolism, and proteolytic activity. On the other hand, the parasites themselves have a role in the outcome of these blood triggered physiological events, consistently using them in their favor. Here, to enlighten the knowledge on vector–pathogen interaction beyond the immune pathways, we will explore different aspects of the vector physiology, discussing how they give support to these long-dated host–parasite relationships.
