Parasitic Helminth Infections Research Articles

Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity

Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

Molecular detection of intestinal parasites in a rural community of Colombia: A one health approach to explore potential environmental-zoonotic transmission.

Protozoan and helminth parasitic infections pose significant public health challenges, especially in developing countries with rural populations marked by suboptimal hygiene practices and socio-economic constraints. The parasites are the etiological agents of these infections and have a notably elevated global prevalence. Therefore, this study focuses on estimating the frequency and transmission dynamics of several parasitic species, including Blastocystis, Giardia, Cryptosporidium spp., Entamoeba histolytica, Ascaris lumbricoides, Trichuris trichiura, Taenia spp. and hookworms, within a rural community in southwest Colombia with a particular emphasis on the One Health framework, considering environmental and zoonotic transmission potentials. This study involved the analysis of 125 samples, encompassing human participants (n = 99), their domestic pets (dogs) (n = 24) and water sources (n = 2). Parasite detection was carried out utilizing a combination of microscopy and molecular techniques. Furthermore, the characterization of Blastocystis subtypes (STs) was achieved through Oxford Nanopore sequencing of the rRNA-18S gene. The investigation also entailed the examination of potential associations between intestinal parasitism and various sociodemographic factors. Results revealed a high frequency of parasitic infections when employing molecular methods, with Blastocystis (n = 109/87%), Giardia (n = 20/16%), Ancylostoma duodenale (n = 28/22%), Ancylostoma ceylanicum (n = 7/5.6%), E. histolytica (n = 6/4.8%), Cryptosporidium spp. (n = 12/9.6%) and even Taenia (n = 1/0.8%) detected. Cryptosporidium spp. was also identified in water samples. Coinfections were prevalent, with 57% (n = 70) of samples exhibiting single-parasite infections and 43% (n = 53) showing various degrees of polyparasitism, emphasizing the complexity of transmission dynamics. Blastocystis subtyping, conducted via Oxford Nanopore sequencing, revealed a diversity of subtypes and coexistence patterns, with ST2 being the most prevalent. This research underscores the importance of using molecular techniques for frequency estimation, particularly emphasizing the relevance of zoonotic transmission in parasitic infections. It highlights the significance of the One Health approach in comprehending the circulation of parasites among animals, humans and environmental sources, thereby directly impacting public health and epidemiological surveillance.

Prevalence of gastrointestinal helminth parasite infections in country chicken from Visakhapatnam district Andhra Pradesh India.

Birds in a free environment carry huge risk of helminth parasite infections affecting the health of poultry and thereby indirectly leading to great economic loss. The present study aimed to evaluate the prevalence, intensity and species diversity of gastrointestinal helminth parasites (GIH) of country chicken (Gallus gallus domesticus) from local chicken markets of Visakhapatnam district, Andhra Pradesh. A total of 300 gastrointestinal tract (GIT) samples were examined from January to December 2021 and the collected parasites were separated, counted, identified and statistically analysed. The overall prevalence of infection was found to be 87% with an intensity of 139.29. The study showed high prevalence with mixed infections (66%), whereas the prevalence with individual groups i.e. cestodes, nematodes and trematodes was found to be 83.00%, 70.33%, and 0.67% respectively. Altogether 10 parasite species were identified viz. Raillietina echinobothrida being the most dominant with a prevalence of 72.67%, followed by Raillietina tetragona (62.00%), Heterakis gallinarum (59.33%), Ascaridia galli (45.33%), Davainea proglottina (43.00%), Amoebotaenia cuneata (42.67%), Raillietina cesticillus (38.33%), Hymenolepis sp. 1 (36.00%), Cotugnia spp. (29.67%) and the least was Hymenolepis sp. 2 (21.00%). In month-wise data, highest prevalence was recorded in July (100%), and the highest seasonal prevalence was recorded in summer (90%), followed by monsoon (87%) and winter (84%). No major significant difference in prevalence was noted between males (88.51%) and females (85.53%). Hosts with high body temperature and low GIT pH levels showed increased prevalence and parasite intensity.

Host gastric corpus microenvironment facilitates Ascaris suum larval hatching and infection in a murine model.

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals.

Interactions between the helminth and intestinal microbiome in smallholder chicken farming systems.

Helminth parasite infections are widespread in smallholder farming systems affecting farmers and livestock animals. There are pathogenic parasites that populate the gut of their host and coexist closely with the gut microbiota. The physical and immunological environment of the gut can be modified by parasites and microbiota creating a wide range of interactions. These interactions modify the development of infection, affects overall host health, and can modify the way a host interacts with its bacterial microbiota. In addition, where there is a high worm burden parasites will affect the health of the host and intestinal tract colonization. This review highlights key studies on the interaction between helminth parasites and the intestinal microbiome to understand the relationship between parasitic worm infections and gut microbiome health in chickens. Finally, the review discusses modulations, molecular changes, and the importance of helminth-microbiome interactions for the host.

Prevalence and Correlates of Soil Transmitted Helminthic Parasitic Infections among Patients in A Tertiary Care Centre in Dibrugarh, Assam

Prevalence and Correlates of Soil Transmitted Helminthic Parasitic Infections among Patients in A Tertiary Care Centre in Dibrugarh, Assam

Current prevalence and geographic distribution of helminth infections in the parasitic endemic areas of rural Northeastern Thailand

BackgroundHelminth infection is a global health issue that not only causes acute helminthiasis but long-term infection may lead to complicated symptoms as well as severe complications. The World Health Organization cooperated with the Ministry of Public Health in many countries, particularly where high prevalence, spending a lot of resources for limiting the infection. In Thailand, the incidence of parasitic helminth infections was continuously declined in the last few decades according to several campaigns for parasitic elimination. However, the rural community in the northeast of Thailand where the highest prevalence of the country still needs to be monitored. This present study aims to report the current prevalence of parasitic helminth infections in Nakhon Ratchasima and Chaiyaphum provinces where sharing a huge area of the northeastern region of Thailand but only a few studies have been published.MethodsThe stool specimens were collected from 11,196 volunteers and processed by modified Kato-Katz thick smear, PBS-ethyl acetate concentration techniques, and PCR. The epidemiological data were collected, analyzed, and used for generating of parasitic hotspots.ResultsThe results indicated that O. viverrini remains the major parasite in this area with a total prevalence of 5.05% followed by Taenia spp., Hookworms, T. trichiura, and Echinostoma spp., respectively. Mueang district of Chaiyaphum province has the highest prevalence especially O. viverrini with a prevalence of 7.15% that higher than the latest national surveillance. Interestingly, the prevalence of O. viverrini was hugely reported (more than 10%) in five subdistricts. The geographic localization of O. viverrini infections revealed that a lot of water reservoirs such as the lakes or branches of the river in the two-most prevalent subdistricts. Our finding indicated that gender and age were insignificantly different.ConclusionThis finding suggested that the parasitic helminth infection in the rural areas of northeast of Thailand remains high and the housing location is a major contributing factor for the parasitic infection.

Evidence and potential drivers of neglected parasitic helminth and protist infections among a small preliminary sample of children from rural Mississippi.

Intestinal infections with helminths (parasitic worms) and protists (single-celled eukaryotes) may be neglected health issues in low-resource communities across the United States. Because they predominantly infect school-aged children and can lead to nutritional deficiencies and developmental delays, these infections can affect lifelong health. More research is needed to understand the prevalence and risk factors of these parasitic infections in the United States. A total of 24 children (ages 0.5-14 years) from a low-resource, rural Mississippi Delta community provided stool samples for 18s rRNA amplification and sequencing to determine infection presence. Parent/guardian interviews provided age, sex, and household size to test for associations with infection. Infections were found in 38% (n= 9) of the samples. 25% (n= 6) of participants were infected with helminths (platyhelminths [n= 5]; nematodes [n= 2]), while 21% (n= 5) were infected with protists (Blastocystis [n= 4]; Cryptosporidium [n= 1]). There were no associations between infection status and age, sex, or household size. Problematically, analytical methods did not allow for more specific classifications for helminth species. These preliminary findings suggest parasitic infections may be overlooked health issues in the rural Mississippi Delta and emphasize the need for more research on potential health outcomes within the United States.

Prevalence of Gastrointestinal Helminths of Dogs and Associated Factors in Hawassa City of Sidama Region, Ethiopia.

A cross-sectional study was carried out in the Sidama region's Hawassa town from March 2021 to July 2021 with the aim of estimating the prevalence and associated factors of dog gastrointestinal helminths. A total of 384 dogs were randomly selected, and their feces were examined using a flotation technique. For data analysis, descriptive statistics and chi-square analyses were employed, and a P-value of less than 0.05 was considered as significant. Accordingly, 56% (n = 215; 95% CI, 49.26-62.66) of dogs had gastrointestinal helminth parasite infection, of which 42.2% (n = 162) had a single infection and 13.8% (n = 53) had a mixed infection. In this study, Strongyloides sp. was the most detected helminth (24.2%), followed by Ancylostoma sp. (15.37%), Trichuris vulpis (14.6%), Toxocara canis (5.73%), Echinococcus sp. (5.47%), and Dipylidium caninum (4.43%). Out of the total sampled dogs tested positive for one or more gastrointestinal helminths, 37.5% (n = 144) were males and 18.5% (n = 71) were females. The total prevalence of helminth infections did not change significantly (P > 0.05) by the gender, age, and breed of dogs. The present study's high prevalence of dog helminthiasis reflects a high occurrence of infection and a concern to the public's health. In light of this conclusion, it is advised that dog owners improve their standards of hygiene. In addition, they should regularly take their animals to veterinary care and frequently administer the appropriate anthelmintics available to their dogs.

Development of a Duplex LAMP Assay with Probe-Based Readout for Simultaneous Real-Time Detection of Schistosoma mansoni and Strongyloides spp. -A Laboratory Approach to Point-Of-Care

Loop-mediated isothermal amplification (LAMP) is the most popular technology for point-of-care testing applications due its rapid, sensitive and specific detection with simple instrumentation compared to PCR-based methods. Many systems for reading the results of LAMP amplifications exist, including real-time fluorescence detection using fluorophore-labelled probes attached to oligonucleotide sequences complementary to the target nucleic acid. This methodology allows the simultaneous detection of multiple targets (multiplexing) in one LAMP assay. A method for multiplexing LAMP is the amplification by release of quenching (DARQ) technique by using a 5'-quencher modified LAMP primer annealed to 3'-fluorophore-labelled acting as detection oligonucleotide. The main application of multiplex LAMP is the rapid and accurate diagnosis of infectious diseases, allowing differentiation of co-infecting pathogens in a single reaction. Schistosomiasis, caused among other species by Schistosoma mansoni and strongyloidiasis, caused by Strongyloides stercoralis, are the most common helminth-parasite infections worldwide with overlapping distribution areas and high possibility of coinfections in the human population. It would be of great interest to develop a duplex LAMP to detect both pathogens in the same reaction. In this study, we investigate the use of our two previously developed and well-stablished LAMP assays for S. mansoni and Strongyloides spp. DNA detection in a new duplex real-time eight-primer system based on a modified DARQ probe method that can be performed in a portable isothermal fluorimeter with minimal laboratory resources. We also applied a strategy to stabilize the duplexed DARQ-LAMP mixtures at room temperature for use as ready-to-use formats facilitating analysis in field settings as point-of-care diagnostics for schistosomiasis and strongyloidiasis.

Prevalence, correlates of undernutrition and intestinal parasitic infection among children below 5 years living in the forest community of Ndelele, East Region of Cameroon: A cross-sectional assessment.

In low- and middle-income countries, undernutrition often co-exists with intestinal parasites, especially Soil Transmitted Helminth (STH) infections in children. The collective impact of both conditions result in undernutrition and can exacerbate the general poor health status of children. A cross-sectional survey of 422 mother-child (12-59 months old) pairs from 14 villages in the District of Ndelele, East Region of Cameroon, was carried out to assess the magnitude and correlates of undernutrition and intestinal parasites. Socio-demographic data were collected from mothers and anthropometric data were collected from children. Parasitological assessment was performed using a combination of direct microscopy flotation, sedimentation and centrifugation techniques. Correlates of undernutrition and intestinal parasites were identified using multinomial logistic regression at individual and household levels. 83.77% of the children assessed for undernutrition were undernourished and 66.82% were positive for one or more intestinal parasites. It was not uncommon for the study participants to be concurrently infected with two or more intestinal parasites. The most common intestinal parasitic infections detected in the study were A. lumbricoides, E. histolytica/dispar and Hookworm infection. Multinomial logistic regression using Nutritional status as outcome showed that, children who were not exclusively breastfed were 106% (RR = 2.06; C.I = 1.12-3.80) more likely to be underweight compared to those who were exclusively breastfed. The household size of 4 to 6 persons also significantly impacted wasting (p-value = 0.007) at 7% (RR = 1.07, C.I = 0.49-2.32). Analysis by a logistic regression model with STH infection as outcome revealed that, Fingernail cleanness (p-value = 0.044; AOR = 1.75; CI = 1.09-2.78) and household size (p-value = 0.038; AOR = 0.55; CI = 0.32-0.92) were positively associated with intestinal parasite infection at the 5% significant level. This study reveals that intestinal helminthic parasitic infections (STH) and undernutrition are serious health problems in children below five in the study area. To address this dire situation, concerted efforts are needed to improve sanitation, hygiene education access, community deworming programs, and improve diets.

Prevalence of Helminth Parasites of Swine in three Selected Local Government Areas of Ibadan, Oyo State, Nigeria

Background: Helminth infections of swine are common, but reports on the economic losses are not available. Though they cause a reduction in weight gain by interfering with food digestion, absorption, and feed conversion efficiency, there has been an increase in feeding cost complicated by helminth parasite infections. The losses are difficult to substantiate due to the chronic nature of helminth infections. This study sought to determine the prevalence and associated risk factors of swine helminth infections in three local government areas of Ibadan, Oyo State, Nigeria. A simple random sampling technique was applied to selected pig farms and animals from three local government areas in Ibadan for participation. 10 grams of freshly voided faeces were collected from a total of 246 pigs into a sterile labelled bottle containing 10% formalin until processed. Faecal samples were examined in the Department of Veterinary Parasitology and Entomology Laboratory, Faculty of Veterinary Medicine, University of Ibadan. Oral interviews were made to assess the daily routine activities and health status of the pigs from farm owners. Results: The overall prevalence of helminth parasites of swine in this study was 34.2% while the species prevalence of four helminth parasites obtained in this study included: A. suum 35 (14.26%), T. suis 23 (9.3%), Oesophagostomum spp 17 (6.9%), and Strongyloides spp 9 (3.6%). Also the overall single and mixed helminth infections were 70.2% and 29.8% in the three local government areas respectively; helminth parasitic load was highest in grower pigs (48.4%), followed by piglets (31.6%), and lowest in adult pigs (22.5%) without significant difference (p>0.05). Female pigs demonstrated a higher parasite burden (37.6%) than male pigs (30.6%) with no significant difference (p>0.05). Semi-intensively managed farms had a higher parasite load (71%) than those under the intensive system (24%) while farms that administered anthelmintic recorded a lower prevalence (15%), and those without had a higher (63%) significance (p<0.05). Pigs in Ona-Ara and Akinyele local government areas voided low (EPG≤100) to moderate (EPG≥100<500) amount of helminth eggs while pigs in Egbeda local government area excreted high (EPG≥500≤1000). Conclusion: The risk factors for helminth infections in pigs are age, sex, farm management practice, and anthelminthic administration.

Prevalence of Intestinal and Urinary Helminth Parasite Infections among ‎Residents of Communities around Lake Alau, Maiduguri

Intestinal and urinary helminth infections affect up to a quarter of the world’s population, with the potential of causing significant public health and economic burden. The occurrence of helminth parasites in stool and urine of residents, and water and soil samples of some communities around Lake Alau, Maiduguri, Nigeria was determined using direct microscopy, floatation and sedimentation techniques. A total of 349 (34.7%) residents were infected out of the 1,005 examined, consisting of 220 (21.9%) males and 129 (12.8%) females, with significant (p<0.05) variation based on gender. Similarly, the infection was significantly (p<0.05) higher among young individuals 197(19.6%) than the adults 152(15.1%). Among the ten communities (Logajiri, Melari, Dumbari, AlauLimanti, Awa Isari, Limanti, Gaskeri, Attakeri, Chellomi and Gomari Karekǝri) examined, the infection was significantly (p<0.05) highest at Gomari Karekǝri 57 (5.7%) and Alau Limanti 55(5.5%) and least at Gaskeri 19 (1.9%) and Chellomari 20 (2.0%). Intestinal parasites encountered consist of Ascaris lumbricoides 234 (23.3%), Trichuris trichiura 24 (2.4%), Strongyloides stercoralis 10 (1.0%), Schistosoma mansoni 8 (0.8%), and Taenia species 1 (0.1%) (p<0.05). Schistosoma haematobium 72 (7.2%) was the only helminth parasite recovered from urine samples examined. Environmental (water and soil) contamination with parasite stages was predominantly with pre-parasitic nematode larvae 50 (25%), eggs of Strongyloides stercoralis 50 (25%), Ascaris lumbricoides 30 (15%), Strongyle spp. 30 (15%) and cysts of protozoans; Entamoeba histolytica 30 (15%) and Giardia intestinalis 10 (5%). The results suggest that infection with intestinal and urinary parasites is common among the residents of the study area and that socio-cultural habits may favour the survival and transmission of these parasites in the area.

Communication is key: Innate immune cells regulate host protection to helminths.

Parasitic helminth infections remain a significant global health issue and are responsible for devastating morbidity and economic hardships. During infection, helminths migrate through different host organs, which results in substantial tissue damage and the release of diverse effector molecules by both hematopoietic and non-hematopoietic cells. Thus, host protective responses to helminths must initiate mechanisms that help to promote worm clearance while simultaneously mitigating tissue injury. The specialized immunity that promotes these responses is termed type 2 inflammation and is initiated by the recruitment and activation of hematopoietic stem/progenitor cells, mast cells, basophils, eosinophils, dendritic cells, neutrophils, macrophages, myeloid-derived suppressor cells, and group 2 innate lymphoid cells. Recent work has also revealed the importance of neuron-derived signals in regulating type 2 inflammation and antihelminth immunity. These studies suggest that multiple body systems coordinate to promote optimal outcomes post-infection. In this review, we will describe the innate immune events that direct the scope and intensity of antihelminth immunity. Further, we will highlight the recent progress made in our understanding of the neuro-immune interactions that regulate these pathways and discuss the conceptual advances they promote.

The role of helminths in the development of non-communicable diseases.

Non-communicable diseases (NCDs) like cardiovascular disease, chronic respiratory diseases, cancers, diabetes, and neuropsychiatric diseases cause significant global morbidity and mortality which disproportionately affect those living in low resource regions including low- and middle-income countries (LMICs). In order to reduce NCD morbidity and mortality in LMIC it is imperative to understand risk factors associated with the development of NCDs. Certain infections are known risk factors for many NCDs. Several parasitic helminth infections, which occur most commonly in LMICs, have been identified as potential drivers of NCDs in parasite-endemic regions. Though understudied, the impact of helminth infections on the development of NCDs is likely related to helminth-specific factors, including species, developmental stage and disease burden. Mechanical and chemical damage induced by the helminth in combination with pathologic host immune responses contribute to the long-term inflammation that increases risk for NCD development. Robust studies from animal models and human clinical trials are needed to understand the immunologic mechanisms of helminth-induced NCDs. Understanding the complex connection between helminths and NCDs will aid in targeted public health programs to reduce helminth-induced NCDs and reduce the high rates of morbidity that affects millions of people living in parasite-endemic, LMICs globally.

Prevalence and Associated Risk Factors of Human Intestinal Helminths Parasitic Infections in Ethiopia: A Systematic Review and Meta-Analysis.

Background Intestinal helminth infections are still public health problems in tropical and subtropical countries including Ethiopia. This review and meta-analysis aimed to produce the pooled prevalence and associated risk factors of human intestinal helminth parasitic infections (HIHPIs) in Ethiopia. Methods Articles written in English were searched from online databases. Sixty-seven studies were included. Meta-analysis was computed using STATA version 14. Result The pooled prevalence of HIHPIs was (33.35%, 95% CI: 28.85%, 37.86%). Ascaris lumbricoides (10.84%, 95% CI: 9.34, 12.34), hookworm spp. (8.89%, 95% CI: 7.75, 10.04), Schistosoma mansoni (4.22%, 95% CI: 3.64, 4.81), Trichuris trichiura (2.51%, 95% CI: 2.17, 2.86), Hymenolepis nana (2.29%, 95% CI: 1.96, 2.63), Taenia species (1.01%, 95% CI: 0.80, 1.22), Strongyloides stercoralis (1.17%, 95% CI: 0.92, 1.41), and Enterobius vermicularis(0.71%, 95% CI: 0.52, 0.90) were recorded. Handwashing before food (OR: 5.22,95% CI: 3.49, 6.94), handwashing after toilet (OR: 3.03, 95%; CI: 1.01, 5.05), age (OR: 1.66, 95% CL. 1.09, 2.23), open defecation (OR: 2.42, 95% CI: 1.60, 3.24), eating raw and unwashed vegetables/fruits (OR: 1.98, 95%; CI: 1.30, 2.66), maternal education (OR: 1.81, 95% CI: 0.91, 2.72), family income (OR: 2.00, 95% CI: 0.87, 3.31), source of drinking water (OR: 3.12, 95% CI: 1.96, 4.27), swimming/contact with river water (OR: 1.90, 95% CI: 1.11, 2.69), barefoot (OR: 3.28, 95% CI: 1.67, 4.88), playing with soil (OR: 2.64, 95% CI: 1.40, 3.88), and family size (OR: 3.75, 95% CI: 2.03, 5.46) were factors associated with HIHPIs in Ethiopia. High heterogeneity of the prevalence of HIHPIs was observed among the studies within and among regions (I2 > 99.6% and P ≤ 0.001). Conclusion HIHPIs in Ethiopia were significantly high. Therefore, special attention should be given by all stakeholders to minimize HIHPIs in Ethiopia.

Novel antiinflammatory biologics shaped by parasite–host coevolution

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen invivo a recombinant cell-free secretome library of helminth-derived immunomodulatory proteins. We successfully expressed 78 recombinant ES proteins from gastrointestinal hookworms and screened the crude invitro translation reactions for anti-IBD properties in a mouse model of acute colitis. After statistical filtering and ranking, 20 proteins conferred significant protection against various parameters of colitis. Lead candidates from distinct protein families, including annexins, transthyretins, nematode-specific retinol-binding proteins, and SCP/TAPS were identified. Representative proteins were produced in mammalian cells and further validated, including ex vivo suppression of inflammatory cytokine secretion by T cells from IBD patient colon biopsies. Proteins identified herein offer promise as novel, safe, and mechanistically differentiated biologics for treating the globally increasing burden of inflammatory diseases.

Suppression of airway allergic eosinophilia by Hp-TGM, a helminth mimic of TGF-β.

Type 2-high asthma is a chronic inflammatory disease of the airways which is increasingly prevalent in countries where helminth parasite infections are rare, and characterized by T helper 2 (Th2)-dependent accumulation of eosinophils in the lungs. Regulatory cytokines such as TGF-β can restrain inflammatory reactions, dampen allergic Th2 responses, and control eosinophil activation. The murine helminth parasite Heligmosomoides polygyrus releases a TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β despite bearing no structural similarity to the mammalian protein. Here, we investigated if Hp-TGM could alleviate allergic airway inflammation in mice exposed to Alternaria alternata allergen, house dust mite (HDM) extract or alum-adjuvanted ovalbumin protein (OVA). Intranasal administration of Hp-TGM during Alternaria exposure sharply reduced airway and lung tissue eosinophilia along with bronchoalveolar lavage fluid IL-5 and lung IL-33 cytokine levels at 24 h. The protective effect of Hp-TGM on airway eosinophilia was also obtained in the longer T-cell mediated models of HDM or OVA sensitisation with significant inhibition of eotaxin-1, IL-4 and IL-13 responses depending on the model and time-point. Hp-TGM was also protective when administered parenterally either when given at the time of allergic sensitisation or during airway allergen challenge. This project has taken the first steps in identifying the role of Hp-TGM in allergic asthma and highlighted its ability to control lung inflammation and allergic pathology. Future research will investigate the mode of action of Hp-TGM against airway allergic eosinophilia, and further explore its potential to be developed as a biotherapeutic in allergic asthma.

Trichinella spiralis nurse cell formation is regulated via CCR7+ dendritic cells.

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells (DCs) and T-cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7-induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis-infected mice. The CCR7-expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7-expressing cells in PLNs increased by more than 30% at 28 days post-infection; however, this increase was significantly inhibited in CCR7-blocked mice treated with CCR7-specific antibodies. T helper 2 (Th2)-and regulatory T (Treg )-related cytokine levels were also reduced by CCR7-specific antibody treatment. CCR7-blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis-specific IgE in the serum were observed in CCR7-blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection-induced suppression of Th2- and Treg -related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and Treg cell responses.

A4 HELMINTH-DERIVED METABOLITES INDUCE A TOLEROGENIC PROFILE IN DENDRITIC CELLS AND ALLEVIATE EXPERIMENTAL COLITIS

BackgroundInflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by abdominal pain, bloody diarrhea, fatigue, weight loss, and diminished quality of life. The morbidity associated with IBD is a result of loss of tolerance towards the gastrointestinal commensal microbiota. The high incidence of IBD in Western societies is inversely correlated with the low incidence of intestinal helminth parasite infections, potentially due to the ability of the helminth parasite to induce tolerance by inducing tolerogenic dendritic cells (tolDC) polarization. Although macromolecules from helminth such as proteins and polysaccharides have been shown to polarize tolDCs, to characterize a novel pathway, in this study we focused on small molecules such as metabolites in the helminth secretome. We hypothesized that helminth-derived metabolites (HDMs) polarize DCs towards a tolerogenic phenotype, which alleviates colitis.AimsTo evaluate and characterize the tolerogenic response induced by HDMs in DCs, and its ability to alleviate colitis.Methods Heligmosomoides polygyrus worms were culture for 24 h and HDMs were isolated from conditioned media by chromatography. Bone marrow dendritic cells (BMDCs) were differentiated with GM-CSF for 8 days and then incubated with HDM for 4 h before LPS stimulation for 20 h. Cytokine secretion was measured by ELISA. The transcriptome of DCs treated with HDMs was assessed by RNAseq. Colitis was induced by giving 3% DSS in drinking water for 5 days followed by 3 days of tap water. The anti-colitic effect of HDMs was assessed by daily treatment with HDM or DCs treated with HDM in the 3 days of tap water.ResultsPre-treatment with HDM decreased LPS-induced TNF and increased IL-10 release by BMDCs, compared to control BMDCs. Colitic mice treated with HDM presented lower disease activity scores, less colon shortening, decreased weight loss, and healthier histopathology compared to vehicle-treated colitic mice. Importantly, there was an increased frequency of CD11c+ CD103+ DCs in the colon of HDM-treated mice, suggesting that HDM alleviates colitis by increasing the abundance of tolDCs in the colon. Adoptive transfer of HDM-treated DCs also reduced the severity of colitis compared with vehicle-treated mice or mice that received naïve DCs. These results indicate that HDM induced tolerogenic DCs, which in turn ameliorates DSS colitis. RNAseq showed that HDM upregulated 183 and downregulated 76 genes. These differentially expressed genes may indicate a novel mechanism by which helminths induce a tolerogenic profile in DCs.ConclusionsHDMs induce tolerogenic DCs and alleviate DSS-induced colitis.Funding AgenciesNSERC and FRQNT