Intestinal Helminths Research Articles

Helminth-derived metabolites induce tolerogenic functional, metabolic, and transcriptional signatures in dendritic cells that attenuate experimental colitis.

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases in which abdominal pain, bloody diarrhea, weight loss, and fatigue collectively result in diminished quality of patient life. The disappearance of intestinal helminth infections in Western societies is associated with an increased prevalence of IBD and other immune-mediated inflammatory diseases. Evidence indicates that helminths induce tolerogenic dendritic cells (tolDCs), which promote intestinal tolerance and attenuate intestinal inflammation characteristic of IBD, but the exact mechanism is unclear. Helminth-derived excretory-secretory (HES) products including macromolecules, proteins, and polysaccharides have been shown to modulate the antigen presenting function of DCs with down-stream effects on effector CD4 + T cells. Previous studies indicate that DCs in helminth-infected animals induce tolerance to unrelated antigens and DCs exposed to HES display phenotypic and functional features of tolDCs. Here, we identify that nonpolar metabolites (HnpM) produced by a helminth, the murine gastrointestinal nematode Heligmosomoides polygyrus bakeri (Hpb), induce tolDCs as evidenced by decreased LPS-induced TNF and increased IL-10 secretion and reduced expression of MHC-II, CD86, and CD40. Furthermore, these DCs inhibited OVA-specific CD4 + T cell proliferation and induced CD4 + Foxp3 + regulatory T cells. Adoptive transfer of HnpM-induced tolDCs attenuated DSS-induced intestinal inflammation characteristic of IBD. Mechanistically, HnpM induced metabolic and transcriptional signatures in BMDCs consistent with tolDCs. Collectively, our findings provide groundwork for further investigation into novel mechanisms regulating DC tolerance and the role of helminth secreted metabolites in attenuating intestinal inflammation associated with IBD. Summary Sentence: Metabolites produced by Heligmosomoides polygyrus induce metabolic and transcriptional changes in DCs consistent with tolDCs, and adoptive transfer of these DCs attenuated DSS-induced intestinal inflammation.

Bacilli load in PTB- intestinal helminths co-infected and PTB non -infected patients at selected public health facilities in Jimma zone, Oromia, Ethiopia: comparative cross-sectional study

BackgroundTuberculosis (TB) and intestinal helminths are diseases that pose a dual burden on public health in low-income countries. Previous studies have shown that helminths can affect the shedding of bacteria or the bacterial load in the sputum of active TB patients. However, there is limited information on bacterial load in TB patients with helminth infections.ObjectiveThis study aimed to compare bacterial load in helminths-infected and non-infected pulmonary tuberculosis patients at selected public health facilities in Jimma zone, Oromia, Ethiopia.MethodsThe study was conducted in Jimma Zone, Oromia, Ethiopia. A facility-based comparative cross-sectional study was employed from August 01, 2020, to January 2021. A total of 124 (55 intestinal helminths-infected and 69 non-infected) newly diagnosed smear-positive pulmonary tuberculosis (PTB) patients were included in the study. A convenience sampling technique was employed to recruit study participants, and a semi-structured questionnaire was used to collect data regarding socio-demographic characteristics and possible risk factors for intestinal helminths co-infection. Stool examination was performed using both wet mount and Kato Katz technique. Additionally, weight and height measurements, sputum, and blood samples were taken to determine body mass index, bacilli load, and diabetic mellitus, respectively. Data were entered into Epi-Data software version 3.1 and analyzed using Statistical Packages for Social Sciences (SPSS) Version 25. A statistically significant difference was defined as a P-value of less than 0.05.ResultsIntestinal helminths reduced bacilli load 3 times more than intestinal helminths non-infected PTB (AOR = 3.44; 95% CI; 1.52, 7.79; P = 0.003) However, diabetes mellitus, HIV, drinking alcohol and cigarette smoking were not associated with bacilli load. The rate of co-infection TB with intestinal helminths was 44%. The three most prevalent parasites detected were Trichuris trichiura 29 (66%), hookworm 19 (43%), and Ascaris lumbricoides 11(25%)). Among co-infected patients about 36 (81.8%) had a single parasite infection, and 19 (43.2%) had multiple infections. A body mass index < 18.5 (AOR = 3.26; 95% CI; 1.25, 8.56;P = 0.016) and untrimmed fingernail status (AOR = 3.63; 95%CI;1.32,9.93;P = 0.012) were significantly associated with PTB- intestinal helminth –co-infection.ConclusionHelminth infection was associated with a lower bacilli load compared to helmenths non-infected PTB. The rate of co-infection TB with intestinal helminths was 44%. Trichuris trichiura was the most prevalent helminth. Untrimmed fingernail and a body mass index were associated with PTB-intestinal helminth co-infection.

Loss of Elp3 blocks intestinal tuft cell differentiation via an mTORC1-Atf4 axis

Intestinal tuft cells are critical for anti-helminth parasite immunity because they produce IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) to expand both goblet and tuft cells. We show that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of Nippostrongylus brasiliensis helminth infection in mice. Elp3 is essential for the generation of intestinal immature tuft cells and for the IL-13-dependent induction of glycolytic enzymes such as Hexokinase 1 and Aldolase A. Importantly, loss of epithelial Elp3 in the intestine blocks the codon-dependent translation of the Gator1 subunit Nprl2, an mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation in response to intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cells and provide insights into promotion of intestinal type 2 immune response to parasites through tRNA modifications.

Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish.

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

Prevalence of Intestinal Helminthes among School-Aged Children in Ife Central Local Government, Nigeria: Implications for Targeted Interventions

Background: Soil-transmitted helminths (STHs) are a major health concern for children in developing countries. This study assesses the prevalence and intensity of STHs among pupils in private nursery and primary schools in Ile-Ife, Nigeria. Methods: The study was conducted in Ife Central LGA, Osun State, Nigeria, involving preschool and school-aged children from two private schools. A total of 55 samples, from 22 male and 33 female pupils, were analyzed for intestinal parasite ova to determine the prevalence of helminth infections among the children. Ethical approval was obtained from the Institute of Public Health, Obafemi Awolowo University, Ile-Ife. Consent was secured from parents or guardians. Samples were processed using the modified Kato-Katz technique and examined microscopically for soil-transmitted helminth (STH) eggs. Data was analyzed using descriptive statistics and chi-square tests, with significance set at p &lt; 0.05. Results: Among the 55 fecal samples collected, the overall prevalence of soil-transmitted helminth (STH) infections was 78.2%. Ascaris lumbricoides were the most prevalent helminth (76.4%), followed by Trichuris trichiuria (14.5%) and hookworms (5.5%). Females had a higher infection rate (81.8%) than males (68.2%). The prevalence of STH infections was highest among pupils aged ≥10 years (81.8%) and lowest among those aged 2-3 years (66.7%). Conclusion: This study highlights a significant burden of STH infections, particularly A. lumbricoides, among schoolchildren in Ile-Ife, Nigeria. The high prevalence necessitates targeted deworming and improved sanitation interventions to reduce the burden of these infections among children in this region.

ФАКТОРЫ ОКРУЖАЮЩЕЙ СРЕДЫ И ЗАРАЖЕННОСТЬ ЛОШАДЕЙ ЖЕЛУДОЧНО-КИШЕЧНЫМИ ГЕЛЬМИНТАМИ В ГОРНОМ АЛТАЕ

The aim of the study is to conduct a comparative assessment of the infestation of horses with intestinal helminths in various administrative districts and to characterize the patterns of the relationship between abiotic and anthropogenic environmental factors and the rates of infestation of horses with intestinal helminths in the Gorny Altai. Based on long-term (2019–2023) ovoscopic examinations of 1.2 thousand horses from 10 districts of the region, the infestation of animals with helminths of the gastrointestinal tract was characterized. Correlation analysis was used to characterize the relationship between the level of infestation of animals with helminths, the number of parasites with abiotic and anthropogenic environmental factors in the context of farms and districts of the Gorny Altai. Horses are mostly infected with helminths in the Chemalsky District, where the prevalence of infestation is 95.8 %, and the infection intensity is 458.3 eggs per gram of feces. The lowest prevalence of helminths in animals was recorded in the Ust-Kansky District – EI 56.3 %, with IIs – 186.7 specimens. g/f. The prevalence of infestation in animals is significantly lower in areas characterized by low temperatures and precipitation, and significantly higher in warmer and more humid areas of the region. The prevalence of infestation in horses is 84.6 %, with IIs – 337.5 specimens. g/f. The most significant factors influencing the infection of animals with intestinal helminths (EI, % and IIs) in farms are the long-term average annual precipitation (r = 0.42 and 0.52) and the degree of anthropogenic pressure (r = –0.55 and –0.63), in the context of regions, long-term average annual temperatures (r = 0.55 and 0.65) and long-term average precipitation (r = 0.69 and 0.65).

Associations of Plasmodium and Intestinal Helminth Infections with Maternal Anemia and Adverse Pregnancy Outcomes in Northwest Ethiopia.

Malaria and intestinal helminth infections are significant public health challenges in Ethiopia. However, little is known about the relationship of Plasmodium and intestinal helminth infections in pregnancy with maternal anemia and adverse pregnancy outcomes. A health-facility-based cross-sectional study was conducted among 526 parturients in northwest Ethiopia to investigate the associations of these parasitic infections with anemia and adverse pregnancy outcomes. Maternal and newborn profiles were collected using questionnaires and checklists. Maternal hematocrit was determined using the micro-hematocrit method. Malaria was diagnosed by microscopy, rapid diagnostic tests, and quantitative polymerase chain reaction, whereas intestinal parasites were detected microscopically using stool wet mount and Kato-Katz preparations. Among the women, 38.6% were anemic, and 36.5% had adverse pregnancy outcomes. Single infections of hookworm (adjusted odds ratio [aOR] = 3.11, 95% CI: 1.64-5.87) in pregnancy were associated with anemia at parturiency, whereas malaria single infections were associated with anemia (aOR = 4.28, 95% CI: 2.17-8.23) and adverse pregnancy outcomes (aOR = 2.94, 95% CI: 1.47-5.91). Moreover, intestinal helminth coinfections in pregnancy were associated with anemia (aOR = 13.3, 95% CI: 4.8-36.8), whereas malaria-helminth coinfections were associated with anemia (aOR = 7.47, 95% CI: 3.71-15.04) and adverse pregnancies (aOR = 4.75, 95% CI: 2.36-9.57). Overall, the study showed that Plasmodium and intestinal helminth infections in pregnancy are associated with anemia and adverse pregnancy outcomes. Thus, strengthening malaria and intestinal parasite infection prevention and control practices in pregnancy is warranted to alleviate the burden of anemia and adverse pregnancy outcomes.

PREVALENCE OF ECTO AND ENDO PARASITES OF WHITE CATFISH (AMEIURUS CATUS) IN UKE RIVER, KARU LOCAL GOVERNMENT AREA OF NASARAWA STATE, NIGERIA

In Uke River, Karu Local Government Area, Nasarawa State, Nigeria, a six-month research was carried out between January and June 2023 to examine the gills and intestinal helminth and protozoan parasites of White Catfish (Ameiurus catus). A total of 100 fresh Ameiurus catus fish samples of both sexes, were obtained from the fishermen and conveyed to the Zoology laboratory of Nasarawa State University for examination. The fishes were processed and examined using gills, oesophagus, intestine and rectum. Twenty-two (22) out of 100 fishes were found to be infected with helminth and protozoan parasites and a total of 31 parasites were isolated belonging to protozoa (Eimeria spp, Hexamita spp, Protoopalina spp), nematode (Procamallanus spp), trematode (Dactylogyrus spp), Cestode (Diphyllobothrium latum, Bothriocephalus claviceps) taxonomic groups. The findings indicated that Ameiurus catus intestine contained a greater quantity of fish parasites (96%). A nematode (Procamallanus spp.) was found to have the highest prevalence of 45.16%. Although the Chi square results showed no significant difference (p&gt;0.05), the prevalence in Ameiurus catus was greater in female samples (63.64%) compared to male samples (36.36%). Fish weighing between 151-200 g (46.14%) and measuring between 21-30 cm (28.57%) had the highest percentage of parasite infection. Going forward, it is imperative to properly cook Ameiurus catus from the Uke River to prevent the spread of parasites to consumers. Additionally, it is advisable to steer clear of any potential actions that could contribute to the parasite predominance near the water body.

Intestinal helminth infections among health examinees: 10-year (2011–2020) nationwide observations in Korea

Intestinal helminth infections among health examinees: 10-year (2011–2020) nationwide observations in Korea

Soil-Transmitted Helminth Infections in Shanghai, China: Surveillance from 2014 to 2023.

Soil-transmitted helminthiasis remains a notable health problem in developing countries. In 1990 in Shanghai, a city in eastern China, 47% of the population was affected. Due to a series of comprehensive approaches, the prevalence decreased to 0.5% in 2009. We collected 10-year surveillance data to assess the epidemic situation of soil-transmitted helminth (STH) infections in Shanghai. Stool samples and questionnaires from participants were collected. The Kato-Katz technique was used to detect infections with Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), and Trichuris trichiura. From 2014 to 2023, a total of 77,685 participants were screened for parasitic infections, and the overall prevalence of STH infections decreased from 0.1% to 0% in Shanghai. Of 77,685 participants, 25 (0.03%) were positive for intestinal helminths, with the most common parasite being A. lumbricoides (72.0%). Generally, elderly participants from rural areas with lower education levels were more likely to be infected with STHs. A total of 2,914 questionnaires were collected, and most respondents (72.6%) had good knowledge about the transmission routes of STHs. However, 12.3% of participants did not know the damage to health caused by STHs, and 19.3% had no idea of how to prevent infection. These data demonstrate the current state of STH infections in Shanghai. The results suggest that various comprehensive measures should be encouraged, continuously implemented, and strengthened accordingly so that STH elimination can be integrated into the Healthy China initiative by 2030.

Intestinal Parasites among Children from Two Communities in Rivers State, Nigeria

A cross-sectional study was conducted on the prevalence of intestinal parasites among children residing in Eagle Island in Port Harcourt Local Government Area and Wiiyaakara in Khana local government all in Rivers State, Nigeria. A total of two hundred and twenty (220) faecal specimens were collected from the children aged (2-17) years into a wide-mouthed universal container and were analyzed using wet saline/iodine and formol ether concentration methods for presence of intestinal parasites. Out of the total of 220 samples examined, 44 children were infected with various intestinal parasites with an overall prevalence of 20%. Eagle Island had a higher prevalence 24(54.5%) than Wiiyaakara, 20(45.5%). The species identified and their prevalence were Ascaris lumbricoides 24(54.6%), Trichuris trichuria13(29.5%) and Hookworm 7(15.9%). The result of this study showed a higher prevalence of infection in male 24(54.5%) than female 20(45.5%) with no significant difference (p&gt;0.05) and children within the age bracket of 10-13 years (27.3%) with the highest prevalence. This study therefore shows that intestinal helminths are prevalent among children residing in Eagle Island and Wiiyaakara Communities in Rivers State. This calls for more enlightenment on measures aimed at reducing parasitic infections among children in these areas, which are associated with poor environmental sanitation and unhygienic personal behaviours among children. Periodic treatment of individual with anti-parasitic drugs should also be encouraged.

Identification of Intestinal Helminths in Cockroaches found in Selected Public Market of Davao City

Identification of Intestinal Helminths in Cockroaches found in Selected Public Market of Davao City

Low schistosomiasis and soil-transmitted helminthiasis prevalence and intensities in selected communities in Davao de Oro and Davao del Norte, the Philippines: A setting for interruption of transmission?

Parasitic neglected tropical diseases, such as schistosomiasis and soil-transmitted helminthiasis (STH), remain as significant public health concerns in developing countries such as the Philippines. This study aimed to determine the prevalence and intensity of schistosomiasis and STH among school-age children (SAC) and adults in two co-endemic provinces in Mindanao in southern Philippines as part of monitoring of national control programs. Stool samples were collected, processed using Kato-Katz technique, and examined microscopically for presence of intestinal helminth ova. A total of 776 SAC and 526 adults participated in the study. Low schistosomiasis prevalence was generally observed in SAC (0.8%) and adults (0.4%). Generally low STH prevalence was reported in both SAC (3.9%) and adults (3.4%). Only three SAC had heavy intensity STH, which was not seen in adults. Results indicate a state of good morbidity control, which may be a result of effective implementation of mass drug administration (MDA) strategy for schistosomiasis, STH, and lymphatic filariasis in the last several years. The low prevalence and intensities of infections may also be partly attributed to the low diagnostic sensitivity of Kato-Katz technique in detecting low intensity intestinal helminth infections. While results of this study also indicate similarly low levels of both these infections in previous studies, sustaining high MDA coverage rates and addressing remaining challenges related to intensified case finding and treatment, improvements in safe water, sanitation, and hygiene, veterinary public health, and vector ecology and management will be necessary to interrupt transmission in these areas.

Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance

Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the "weep" response that is critical for type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here, we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.

Prevalence of Intestinal Helminths Among Mogadishu Residents Attending Somali Sudanese Specialized Hospital, Mogadishu, Somalia

Intestinal helminths infection remains a public health concern in the developing countries. Over 1.5 billion people on a global scale are infected with one or more intestinal helminths. Sub - Saharan Africa is considered among the most affected areas with helminths infections. These infection rates are linked with factors such as socioeconomic status, personal hygiene, overcrowding and poor waste management. This study aimed to investigate the frequency of intestinal helminths infections among Mogadishu residents attending Somali Sudanese specialized hospital. The presented study was designed as a descriptive cross - sectional hospital - based study conducted at Somali Sudanese specialized hospital at Mogadishu, Somalia, during the period from November 2022 to April 2023. Stool samples were collected from 1865 Mogadishu residents attending Somali Sudanese Specialized Hospital. Helminths infections were confirmed by identification of the diagnostic stage of the parasite under light microscope. The study findings indicated that the prevalence of intestinal helminths was 2.0%. The distribution of the parasitic infections was 0.7%, 0.6%, 0.4%, 0.3% (Trichuris trichiura, Enterobius vermicularis, Hymenolepis nana, and Ascaris lumbricoides) respectively. This result showed that the most common infection is caused by Trichuris trichiura followed by Enterobius vermicularis with Ascaris lumbricoides being the least common. The high prevalence of intestinal helminths infections among Mogadishu residents highlights a poor personal hygiene.

Modulation of the rat intestinal microbiota in the course of Anisakis pegreffii infection.

Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.

A new superhero, the intraepithelial mast cell, joins the “Guardians of the Gut”

A new superhero, the intraepithelial mast cell, joins the “Guardians of the Gut”

Intestinal helminth infection impairs vaccine-induced T cell responses and protection against a SARS-CoV-2 Omicron variant in mice

Abstract Although vaccines have reduced the global COVID-19 disease burden, the impact of gastrointestinal helminth infection on their efficacy in endemic regions of the world remains uncertain. Here, using Heligmosomoides polygyrus bakeri (Hpb), a model, non-invasive murine intestinal hookworm, we evaluated whether Hpb infection affects the efficacy of mRNA S6P, a preclinical vaccine encoding a hexaproline stabilized spike of the Wuhan-1 strain of SARS-CoV-2. In the setting of Hpb infection, immunization of mRNA S6P generated equivalent serum antibody and antigen-specific B cell responses. However, antigen-specific CD4+ and CD8+ T cell responses were reduced compared to mice immunized without Hpb infection. Helminth infection did not skew vaccine-induced T cell responses but rather inhibited their capacity to produce polyfunctional cytokines. Hpb infection caused similar T cell defects in mice immunized with an approved adenoviral vectored SARS-CoV-2 vaccine (Ad26.COV2.S). Challenge experiments showed that although Hpb-infected mice vaccinated with mRNA S6P were fully protected against the ancestral SARS-CoV-2 strain WA1/2020, there was a loss of vaccine-mediated protection against Omicron variant BA5.5 compared to animals immunized in the absence of Hpb infection. These results in mice suggest that intestinal helminth infection can compromise T cell responses and protective efficacy of vaccines against SARS-CoV-2 variants that escape neutralizing antibody responses.

Maternal Infection and altered fetal immune programming.

Abstract The maternal-fetal interface involves complex and balanced interactions between mother and fetus, which support the development of the fetal immune system. While we know maternal helminth infection during pregnancy is known to disrupt this relationship and affect neonatal immune development, the fundamental mechanisms that drive fetal immune programming is not completely understood. To further examine how maternal parasitic infection influences offspring immunity, we established a model in which female mice prior to mating are infected with the persistent mouse intestinal helminth, Heligmosomoides polygyrus (HP). One week after infection, female mice are mated, and the progeny are aged to adulthood. The offspring are then challenged with influenza virus. Intriguingly, we found that offspring born from mothers with HP infections were less susceptible to influenza challenge than offspring born from uninfected mothers. This data implies that the effects of maternal helminth infection are long lasting, and potentially involve fetal programming during the early development of the immune system.

Modulation of intestinal epithelial permeability by chronic small intestinal helminth infections.

Increased permeability of the intestinal epithelial layer is linked to the pathogenesis and perpetuation of a wide range of intestinal and extra-intestinal diseases. Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed as a treatment for many of the same diseases. Helminths induce immunoregulatory changes in their host which could decrease epithelial permeability, which is highlighted as a potential mechanism through which helminths treat disease. Despite this, the influence of a chronic helminth infection on epithelial permeability remains unclear. This study uses the chronically infecting intestinal helminth Heligmosomoides polygyrus to reveal alterations in the expression of intestinal tight junction proteins and epithelial permeability during the infection course. In the acute infection phase (1 week postinfection), an increase in intestinal epithelial permeability is observed. Consistent with this finding, jejunal claudin-2 is upregulated and tricellulin is downregulated. By contrast, in the chronic infection phase (6 weeks postinfection), colonic claudin-1 is upregulated and epithelial permeability decreases. Importantly, this study also investigates changes in epithelial permeability in a small human cohort experimentally challenged with the human hookworm, Necator americanus. It demonstrates a trend toward small intestinal permeability increasing in the acute infection phase (8 weeks postinfection), and colonic and whole gut permeability decreasing in the chronic infection phase (24 weeks postinfection), suggesting a conserved epithelial response between humans and mice. In summary, our findings demonstrate dynamic changes in epithelial permeability during a chronic helminth infection and provide another plausible mechanism by which chronic helminth infections could be utilized to treat disease.