The Role of the Intestinal Epithelium in the “Weep and Sweep” Response during Gastro—Intestinal Helminth Infections

Helminths are metazoan parasites infecting around 1.5 billion people all over the world. During coevolution with hosts, worms have developed numerous ways to trick and evade the host immune response, and because of their size, they cannot be internalized and killed by immune cells in the same way as bacteria or viruses. During infection, a substantial Th2 component to the immune response is evoked which helps restrain Th1-mediated tissue damage. Although an enhanced Th2 response is often not enough to kill the parasite and terminate an infection in itself, when tightly coordinated with the nervous, endocrine, and motor systems it can dislodge parasites from tissues and expel them from the gut. A significant role in this “weep and seep” response is attributed to intestinal epithelial cells (IEC). This review highlights the role of various IEC lineages (enterocytes, tuft cells, Paneth cells, microfold cells, goblet cells, and intestine stem cells) during the course of helminth infections and summarizes their roles in regulating gut architecture and permeability, and muscle contractions and interactions with the immune and nervous system.

Daily rhythms in gene expression of the human parasite Schistosoma mansoni

Background The consequences of the earth’s daily rotation have led to 24-h biological rhythms in most organisms. Even some parasites are known to have daily rhythms, which, when in synchrony with host rhythms, can optimise their fitness. Understanding these rhythms may enable the development of control strategies that take advantage of rhythmic vulnerabilities. Recent work on protozoan parasites has revealed 24-h rhythms in gene expression, drug sensitivity and the presence of an intrinsic circadian clock; however, similar studies on metazoan parasites are lacking. To address this, we investigated if a metazoan parasite has daily molecular oscillations, whether they reveal how these longer-lived organisms can survive host daily cycles over a lifespan of many years and if animal circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni that lives in the vasculature for decades and causes the tropical disease schistosomiasis. Results Using round-the-clock transcriptomics of male and female adult worms collected from experimentally infected mice, we discovered that ~ 2% of its genes followed a daily pattern of expression. Rhythmic processes included a stress response during the host’s active phase and a ‘peak in metabolic activity’ during the host’s resting phase. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include predicted drug targets and a vaccine candidate. These 24-h rhythms may be driven by host rhythms and/or generated by a circadian clock; however, orthologs of core clock genes are missing and secondary clock genes show no 24-h rhythmicity. Conclusions There are daily rhythms in the transcriptomes of adult S. mansoni, but they appear less pronounced than in other organisms. The rhythms reveal temporally compartmentalised internal processes and host interactions relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other animals. We have shown which transcripts oscillate at this temporal scale and this will benefit the development and delivery of treatments against schistosomiasis.

Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae

Extracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni—infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1’s role in shaping schistosome EV function and definitive host relationships.

Low-level pathogen transmission from wild to farmed salmonids in a flow-through fish farm

While the potential effects of pathogens spread from farmed fish to wild populations have frequently been studied, evidence for the transmission of parasites from wild to farmed fish is scarce. In the present study, we evaluated natural bacterial and parasitic infections in brown trout (Salmo trutta m. fario) collected from the Černá Opava river (Czech Republic) as a potential source of infections for rainbow trout (Oncorhynchus mykiss) reared in a flow-through farm system fed by the same river. The prevalence of bacterial and protozoan infections in farmed fish was comparable, or higher, than for riverine fish. Despite this, none of the infected farmed fish showed any signs of severe diseases. Substantial differences in metazoan parasite infections were observed between wild and farmed fish regarding monogeneans, adult trematodes, nematodes, the myxozoan Tetracapsuloides bryosalmonae found in riverine fish only, and larval eye-fluke trematodes sporadically found in farmed fish. The different distribution of metazoan parasites between brown and rainbow trout most probably reflects the availability of infected intermediate hosts in the two habitats. Despite the river being the main water source for the farm, there was no significant threat of parasite infection to the farmed fish from naturally infected riverine fish.

Pathogens co-transported with invasive non-native aquatic species: implications for risk analysis and legislation

Invasive Non-Native Species (INNS) can co-transport externally and internally other organisms including viruses, bacteria and other eukaryotes (including metazoan parasites), collectively referred to as the symbiome. These symbiotic organisms include pathogens, a small minority of which are subject to surveillance and regulatory control, but most of which are currently unscrutinized and/or unknown. These putatively pathogenetic symbionts can potentially pose diverse risks to other species, with implications for increased epidemiological risk to agriculture and aquaculture, wildlife/ecosystems, and human health (zoonotic diseases). The risks and impacts arising from co-transported known pathogens and other symbionts of unknown pathogenic virulence, remain largely unexplored, unlegislated, and difficult to identify and quantify. Here, we propose a workflow using PubMed and Google Scholar to systematically search existing literature to determine any known and potential pathogens of aquatic INNS. This workflow acts as a prerequisite for assessing the nature and risk posed by co-transported pathogens of INNS; of which a better understanding is necessary to inform policy and INNS risk assessments. Addressing this evidence gap will be instrumental to devise an appropriate set of statutory responsibilities with respect to these symbionts, and to underpin new and more effective legislative processes relating to the disease screening and risk assessment of INNS.

Multifunctional Fructose 1,6-Bisphosphate Aldolase as a Therapeutic Target

Fructose 1,6-bisphosphate aldolase is a ubiquitous cytosolic enzyme that catalyzes the fourth step of glycolysis. Aldolases are classified into three groups: Class-I, Class-IA, and Class-II; all classes share similar structural features but low amino acid identity. Apart from their conserved role in carbohydrate metabolism, aldolases have been reported to perform numerous non-enzymatic functions. Here we review the myriad “moonlighting” functions of this classical enzyme, many of which are centered on its ability to bind to an array of partner proteins that impact cellular scaffolding, signaling, transcription, and motility. In addition to the cytosolic location, aldolase has been found the extracellular surface of several pathogenic bacteria, fungi, protozoans, and metazoans. In the extracellular space, the enzyme has been reported to perform virulence-enhancing moonlighting functions e.g., plasminogen binding, host cell adhesion, and immunomodulation. Aldolase’s importance has made it both a drug target and vaccine candidate. In this review, we note the several inhibitors that have been synthesized with high specificity for the aldolases of pathogens and cancer cells and have been shown to inhibit classical enzyme activity and moonlighting functions. We also review the many trials in which recombinant aldolases have been used as vaccine targets against a wide variety of pathogenic organisms including bacteria, fungi, and metazoan parasites. Most of such trials generated significant protection from challenge infection, correlated with antigen-specific cellular and humoral immune responses. We argue that refinement of aldolase antigen preparations and expansion of immunization trials should be encouraged to promote the advancement of promising, protective aldolase vaccines.

Intestinal Parasites of Neotropical Wild Jaguars, Pumas, Ocelots, and Jaguarundis in Colombia: Old Friends Brought Back from Oblivion and New Insights

Neotropical wild felids (NWF) are obligate carnivore species present in Central and South America, and some are considered endangered due to constantly decreasing populations. NWF can become infected by a wide range of protozoan and metazoan parasites, some of them affecting their health conditions and others having anthropozoonotic relevance. Parasitological studies on NWF are still very scarce, and most data originated from dead or captive animals. On this account, the current study aimed to characterize gastrointestinal parasites of free-ranging jaguars (Panthera onca), pumas (Puma concolor), ocelots (Leopardus pardalis), and jaguarundis (Herpailurus yagouaroundi), i.e., four out of six NWF species endemic to Colombia. Fecal samples from jaguars (n = 10) and ocelots (n = 4) were collected between 2012 and 2017 as part of the Jaguar Corridor Initiative from six geographic locations in Colombia. In addition, cestode specimens were obtained during puma and jaguarundi necropsies. Scat samples were processed by standardized sodium acetate-acetic acid-formalin (SAF), sedimentation, and flotation techniques and by carbol fuchsin-stained fecal smears. Morphological evaluation of feces showed the presence of one cestode (Spirometra sp.), a nematode (Toxocara cati), an acanthocephalan (Oncicola sp.), and one cyst-forming coccidian (Cystoisospora-like oocysts). Feces oocysts were submitted to a Toxoplasma gondii-specific PCR for species identification, but no product was amplified. The cestodes isolated from a puma and jaguarundi were molecularly characterized by sequencing cytochrome c oxidase subunit I, identifying them as Taenia omissa and as a T. omissa sister lineage, respectively. These results collectively demonstrate the potential role of NWF as natural reservoir hosts for neglected zoonotic parasites (e.g., Spirometra sp., T. cati) and highlight their possible role in parasite transmission to human communities. Due to public health concerns, the occurrence of these parasites should be monitored in the future for appropriate zoonotic management practices in conservation strategies and wild felid health management programs.

Stages of Granulomatous Response Against Histozoic Metazoan Parasites in Mullets (Osteichthyes: Mugilidae)

Histozoic parasite–fish host interaction is a dynamic process that leads to the formation of a granuloma, a specific chronic inflammatory response with discernible histological features. Mullets (Osteichthyes: Mugilidae) represent a suitable model concerning the development of such lesions in the host–parasite interface. The present work aimed to identify granuloma developmental stages from the early to the late phase of the infection and to characterize the immune cells and non-inflammatory components of the granuloma in different stages. For this purpose, 239 mullets were collected from 4 Sardinian lagoons, and several organs were examined by combining histopathological, bacteriological, and immunohistochemical methods. Granulomas associated with trematode metacercariae and myxozoan parasites were classified into three developmental stages: (1) pre-granuloma stage, characterized by intact encysted parasite and with no or mild tissue reaction; (2) intermediate stage, with partially degenerated parasites, necrosis, and a moderate number of epithelioid cells (ECs); and (3) late stage, with a necrotic core and no detectable parasite with a high number of ECs and fibroblasts. The three-tier staging and the proposed morphological diagnosis make it conceivable that histopathology could be an essential tool to evaluate the granulomas associated with histozoic parasitic infection in fish.

Pathogens co-transported with invasive non-native aquatic species: implications for risk analysis and legislation

Invasive Non-Native Species (INNS) can co-transport externally and internally other organisms including viruses, bacteria and other eukaryotes (including metazoan parasites), collectively referred to as the symbiome. These symbiotic organisms include pathogens, a small minority of which are subject to surveillance and regulatory control, but most of which are currently unscrutinised and/or unknown. The (putatively) pathogenic symbionts co-transported by an INNS host may be latent or associated with asymptomatic infection and unable to cause disease in the INNS, but may be opportunistic pathogens of other hosts, causing impact to one or more hosts in their new range. These pathogens potentially pose diverse risks to other species, with implications for increased epidemiological risk to agriculture and aquaculture, wildlife/ecosystems, and human health (zoonotic diseases). Aquatic INNS and their symbionts have many introduction pathways, including commodity and trade (releases, escapes, contaminant), transport (stowaway), and dispersal (corridor, unaided). The risks and impacts arising from co-transported pathogens, including other symbionts of unknown pathogenic virulence, remain largely unexplored, unlegislated, and difficult to identify and quantify. Here, we propose a workflow to determine any known and potential pathogens of aquatic INNS. This workflow acts as a prerequisite for assessing the nature and risk posed by co-transported symbionts of INNS. A better understanding of co-transported organisms, the risks they pose and their impact, is necessary to inform policy and INNS risk assessments. This leap in evidence will be instrumental to devise an appropriate set of statutory responsibilities with respect to these symbionts, and to underpin new and more effective legislative processes relating to the disease screening and risk assessment of INNS.

A Visitor of Tropical Waters: First Record of a Clymene Dolphin (Stenella clymene) Off the Patagonian Coast of Argentina, With Comments on Diet and Metazoan Parasites

The poorly known Clymene dolphin (Stenella clymene) is a small oceanic cetacean distributed in tropical and subtropical waters of the Atlantic Ocean. In this study, we report, for the first time, a vagrant individual of Clymene dolphin in Argentina (Rada Tilly) that represents the current southern-most record for this cetacean species. We provide a molecular identification of the dolphin, based on partial sequences of the mitochondrial cytochrome b gene, generated from DNA extracted from its metazoan parasites. Three prey species, namely Argentine hake, Patagonian squid and lobster krill were identified from hard pieces collected in the stomach. Seven metazoan parasite taxa (three in adult stage, one immature stage and three in larval stage) were identified using morphological and molecular data, i.e., the digenean Pholeter gastrophilus (new host record), the cestodes Tetrabothrius (Tetrabothrius) forsteri, Clistobothrium grimaldii unidentified phyllobothriid plerocercoids, the nematodes Anisakis pegreffii (new host record), Halocercus delphini and the acanthocephalan Corynosoma australe (new host record). Our study provides the first molecular exploration of the metazoan parasite diversity in delphinids from the southwestern Atlantic, and contributes significantly to understand the poorly known parasite fauna of the Clymene dolphin.