Soil-transmitted helminths: A critical review of the impact of co-infections and implications for control and elimination.

Researchers have raised the possibility that soil-transmitted helminth (STH) infections might modify the host's immune response against other systemic infections. STH infections can alter the immune response towards type 2 immunity that could then affect the likelihood and severity of other illnesses. However, the importance of co-infections is not completely understood, and the impact and direction of their effects vary considerably by infection. This review synthesizes evidence regarding the relevance of STH co-infections, the potential mechanisms that explain their effects, and how they might affect control and elimination efforts. According to the literature reviewed, there are both positive and negative effects associated with STH infections on other diseases such as malaria, human immunodeficiency virus (HIV), tuberculosis, gestational anemia, pediatric anemia, neglected tropical diseases (NTDs) like lymphatic filariasis, onchocerciasis, schistosomiasis, and trachoma, as well as Coronavirus Disease 2019 (COVID-19) and human papillomavirus (HPV). Studies typically describe how STHs can affect the immune system and promote increased susceptibility, survival, and persistence of the infection in the host by causing a TH2-dominated immune response. The co-infection of STH with other diseases has important implications for the development of treatment and control strategies. Eliminating parasites from a human host can be more challenging because the TH2-dominated immune response induced by STH infection can suppress the TH1 immune response required to control other infections, resulting in an increased pathogen load and more severe disease. Preventive chemotherapy and treatment are currently the most common approaches used for the control of STH infections, but these approaches alone may not be adequate to achieve elimination goals. Based on the conclusions drawn from this review, integrated approaches that combine drug administration with water, sanitation and hygiene (WASH) interventions, hygiene education, community engagement, and vaccines are most likely to succeed in interrupting the transmission of STH co-infections. Gaining a better understanding of the behavior and relevance of STH co-infections in the context of elimination efforts is an important intermediate step toward reducing the associated burden of disease.

Helminth and ectoparasitic faunas of the Harris's hawk, Parabuteo unicinctus (Accipitriformes: Accipitridae), in Chile: new data on host-parasite associations for Neotropical raptors / Helmintos e ectoparasitas do gavião-asa-de-telha (Accipitriformes: Parabuteo unicinctus) no Chile: novas associações parasita-hospedeiro para os rapinantes neotropicais

Abstract Birds of prey harbor a wide spectrum of various parasites, mostly with a heteroxenous life cycle. However, most reports on their parasites come from Europe. Although the Harris's hawk (Parabuteo unicinctus) is a widespread species in America, parasitological surveys on this hawk are mostly focused on coprological findings and ectoparasites, with poor attention paid to helminths. The aim of this study was to gather new and additional data on host-parasite associations for the Harris's hawk. Twenty-nine birds from central and southern Chile were necropsied. Further, nine birds from a rehabilitation center and 22 museum specimens were inspected for ectoparasites. Sixty-eight percent of birds hosted at least one parasite species. Four lice species, one mite species and eight helminth species (five nematodes, two platyhelminthes and one acanthocephalan) were recorded. Parasitic lice Colpocephalum nanum and Nosopon chanabense, and a nematode Cyathostoma (Hovorkonema) americana were recorded for the first time in raptors from the Neotropics. A feather mite, Pseudalloptinus sp., nematodes, Physaloptera alata and Microtetrameres sp., and a trematode Neodiplostomim travassosi, were recorded for the first time in Chile. The presence of diverse heteroxenous helminths reported here in the Harris's hawk could be explained by the generalist diet of this raptor.

Resumo As aves de rapina representam uma fonte importante de parasitas heteroxenos. Porém, a maioria dos relatos são da Europa. O gavião-asa-de-telha (Parabuteo unicinctus) é uma espécie amplamente distribuída no continente Americano, porém estudos parasitológicos nessas aves têm documentado achados coprológicos e ectoparasitas, com poucos relatos sobre endoparasitas como helmintos. Por essa razão, o objetivo deste estudo foi descrever novas associações parasita-hospedeiro para o gavião-asa-de-telha e rapinantes neotropicais. Vinte nove aves provenientes do centro e sul do Chile foram submetidas à necropsia. Por outro lado, nove aves de um centro de reabilitação e 22 espécimes de museu foram inspecionados em busca de ectoparasitas. Do total de aves, 68,3% foram identificadas como portadoras de pelo menos uma espécie de parasita. Quatro espécies de piolhos, um ácaro e oito helmintos (cinco nematoides, dois platelmintos e um acantocéfalo) foram registrados. Os piolhos Colpocephalum nanum, Nosopon chanabense e o nematóide Cyathostoma (Hovorkonema) americana são reportados pela primeira vez em rapinantes neotropicais. Colpocephalum nanum, N. chanabense, Pseudalloptinus sp., Physaloptera alata, Microtetrameres sp., C. (H.) americana e Neodiplostomim travassosi, são reportados pela primeira vez no Chile. A diversidade de helmintos heteróxenos, identificados neste trabalho, poderia ser explicada devido à dieta geralista do gavião-asa-de-telha.

Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate.

Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC diversity and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene diversity gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, correlative evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC diversity and microbial flora as contributing factors of parasite infection.

Macrophage regulation & function in helminth infection.

Macrophages are innate immune cells with essential roles in host defense, inflammation, immune regulation and repair. During infection with multicellular helminth parasites, macrophages contribute to pathogen trapping and killing as well as to tissue repair and the resolution of type 2 inflammation. Macrophages produce a broad repertoire of effector molecules, including enzymes, cytokines, chemokines and growth factors that govern anti-helminth immunity and repair of parasite-induced tissue damage. Helminth infection and the associated type 2 immune response induces an alternatively activated macrophage (AAM) phenotype that - beyond driving host defense - prevents aberrant Th2 cell activation and type 2 immunopathology. The immune regulatory potential of macrophages is exploited by helminth parasites that induce the production of anti-inflammatory mediators such as interleukin 10 or prostaglandin E2 to evade host immunity. Here, we summarize current insights into the mechanisms of macrophage-mediated host defense and repair during helminth infection and highlight recent progress on the immune regulatory crosstalk between macrophages and helminth parasites. We also point out important remaining questions such as the translation of findings from murine models to human settings of helminth infection as well as long-term consequences of helminth-induced macrophage reprogramming for subsequent host immunity.

Parasitic helminth infections in humans modulate Trefoil Factor levels in a manner dependent on the species of parasite and age of the host.

Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33) -driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection in females, not Schistosoma or co-infection. This elevation was correlated with age, but not worm burden. TFF3 was elevated by Schistosoma infection and found to be generally higher in females. IL-33 was not significantly altered by infection. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels (IFNγ, TNFα, IL-33, IL-13, IL-1ß, IL-17A, IL-22, and IL-10) in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, likely in an age dependent manner. In the serum, only IL-10 and IL-13 were significantly increased, while in urine IFN-γ, TNF-α, IL-13, IL-1ß, IL-22, and IL-10 were significantly increased in by infection. Taken together, these data support a role for TFF proteins in human helminth infection.

Efficacy of Mebendazole and Praziquantel against Soil-Transmitted Helminths and Schistosoma mansoni Infections among Schoolchildren in Northwest Ethiopia.

BACKGROUND: Soil-transmitted helminths (STHs) and Schistosoma mansoni are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited. OBJECTIVE: This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and Schistosoma mansoni parasites. METHODS: A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for Schistosoma mansoni with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and S. mansoni parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel. RESULTS: Among 422 participants, the prevalence of STHs, hookworm, Ascaris lumbricoides, and S. mansoni was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against A. lumbricoides increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against S. mansoni-infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs. CONCLUSION: The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and A. lumbricoides are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat S. mansoni. Therefore, single-dose praziquantel to S. mansoni and redosing of single-dose mebendazole to A. lumbricoides and hookworm infections can be used for treatment purposes.

Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis.

Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.

Field and Laboratory Observations on the Life History of Gordius terrestris (Phylum Nematomorpha), A Terrestrial Nematomorph.

To date, all free-living adult hairworms have been reported from aquatic habitats. However, in Oklahoma, a recently described gordiid, Gordius terrestris, is consistently encountered in terrestrial habitats. We found this gordiid species has a unique egg morphology, unlike that of any other hairworm species, with an outer shell separated by distinct space from a thick inner membrane surrounding the developing larva. Because of this unique egg morphology and the occurrence of free-living hairworms in terrestrial habitats, it was hypothesized that G. terrestris represents the first report of a hairworm species with a terrestrial life cycle. In this study, we observed thousands of free-living adult worms in terrestrial habitats such as wet lawns and underneath wet sod during the winter. We found evidence of worms mating in these terrestrial habitats, followed by female worms burrowing and ovipositing in the soil. In the laboratory, significantly more females burrowed in the soil than males, providing a plausible explanation for the extreme male-biased sex ratio observed for free-living worms found on wet lawns. Finally, we collected terrestrial earthworms infected with the cyst stage of this gordiid species in the field and confirmed those observations by infecting earthworms with G. terrestris larvae in the laboratory. Taken together, these observations strongly support the hypothesis that G. terrestris has a terrestrial life cycle.

Parasites of the Shiny Cowbird, Molothrus bonariensis, and the Austral Blackbird, Curaeus curaeus, (Passeriformes: Icteridae) in Chile / Parasitas do chupim Molothrus bonariensis e do pássaro-preto-austral Curaeus curaeus (Passeriformes: Icteridae) no Chile

Abstract Comparative studies of parasites in sympatric bird species have been generally scarce. Parasitic infection/transmission can be spread in a number of ways that suggests possible direct and indirect, horizontal transmission between avian hosts. In order to determine whether two sympatric icterids from Central and Southern Chile share their parasite fauna (ecto- and endoparasites), we examined parasites of 27 Shiny Cowbirds, Molothrus bonariensis, and 28 Austral Blackbirds, Curaeus curaeus, including individuals captured in the wild and carcasses. We found that Shiny Cowbirds were infected with the chewing lice Brueelia bonariensis, Philopterus sp. 1, the feather mites Amerodectes molothrus, Proctophyllodes spp. (species 1 and 2), and the helminths Mediorhynchus papillosus, Plagiorhynchus sp., Dispharynx nasuta and Tetrameres paucispina, while Austral Blackbirds had the chewing lice Myrsidea sp., Philopterus sp. 2, the feather mites Proctophyllodes sp. 3, Amerodectes sp., and three helminths: Anonchotaenia sp., Capillaria sp. and M. papillosus. The flea Dasypsyllus (Neornipsyllus) cteniopus was found only on the Austral Blackbird. The only parasite species shared by both icterids was the acanthocephalan M. papillosus, possibly due to their feeding on the same intermediate insect hosts. With the exception of B. bonariensis and Philopterus sp. 1 found on the Shiny Cowbird, all species reported in this study represent new parasite-host associations and new records of parasite diversity in Chile.

Resumo Estudos comparativos de parasitas em espécies de aves simpátricas são escassos. A infecção/transmissão de parasitas pode acontecer de diversas maneiras, incluindo possível transmissão direta, indireta ou horizontal entre as aves hospedeiras. Com o objetivo de determinar se dois icterídeos simpátricos do centro e sul do Chile compartilham a sua fauna parasitária (ecto- e endoparasitas), foram examinados os parasitas de 27 chupins Molothrus bonariensis e 28 pássaros-pretos-austral Curaeus curaeus, incluindo indivíduos capturados com rede de neblina e em carcaças. Nos chupins analisados, foram encontrados os piolhos de penas Brueelia bonariensis, Philopterus sp. 1, os ácaros Amerodectes molothrus, Proctophyllodes spp. (espécie 1 e 2), e os helmintos Mediorhynchus papillosus, Plagiorhynchus sp., Dispharynx nasuta e Tetrameres paucispina. Em contraste, os pássaros-pretos-austral estavam infectados com os piolhos Myrsidea sp., Philopterus sp. 2, os ácaros Proctophyllodes sp. 3, Amerodectes sp., e os helmintos Anonchotaenia sp., Capillaria sp. e M. papillosus. Adicionalmente, um espécime de pássaro-preto-austral estava parasitado pela pulga Dasypsyllus (Neornipsyllus) cteniopus. A única espécie de parasita que foi encontrada nas duas espécies de aves foi o acantocéfalo M. papillosus, possivelmente devido ao fato de que ambas as aves se alimentam dos insetos que são os hospedeiros intermediários deste parasita. Exceto os registros de B. bonariensis e Philopterus sp. 1 encontrados no chupim, todas as espécies reportadas neste estudo correspondem à novas associações de parasita/hospedeiro e novos registros para a diversidade parasitológica do Chile.

First report of the intestinal helminth community in the broad-headed spiny-rat Clyomys laticeps (Rodentia, Echimyidae) / Primeiro registro da comunidade de helmintos intestinais do rato de espinho Clyomys laticeps (Rodentia, Echymyidae)

Abstract The broad-headed spiny rat, Clyomys laticeps, is an echimyid rodent found in open areas of Cerrado and Pantanal biomes in central Brazil and Paraguay. Little is known about the parasites associated with this semi-fossorial species, as no previous studies have been conducted on their helminth fauna. The aim of this study was to report the helminth community structure of C. laticeps inhabiting Serra de Caldas Novas State Park, a Cerrado area in central Brazil. Trappings were carried out in dry grasslands from January to October 2016, and the large and small intestines of 14 C. laticeps individuals were examined for the presence of helminths. Three nematode species were found: Fuellebornema almeidai, Pterygodermatites (Paucipectines) sp., and Subulura forcipata, and 85.7% of the studied species were infected with at least one of these helminths. F. almeidai was the most prevalent species among hosts, and S. forcipata was the most abundant. This study is the first report on helminth community structure in C. laticeps. We report a new host species and increase the known geographical range of F. almeidai, and provide the first record of Pterygodermatites (Paucipectines) sp. infecting echimyids. This is also the first report of S. forcipata in a mammal host.

Resumo Clyomys laticeps é um roedor equimídeo encontrado em áreas abertas dos biomas Cerrado e Pantanal, ao longo do Brasil central e Paraguai. Essa espécie apresenta hábitos semi-fossoriais e atividade noturna. Até o momento, não existem estudos sobre seus parasitas. O objetivo deste trabalho foi descrever a comunidade de helmintos encontrados em C. laticeps, capturados no Parque Estadual da Serra de Caldas Novas, uma área de Cerrado no Brasil Central. Os indivíduos foram capturados em área de "campo sujo" entre janeiro e outubro de 2016. Os intestinos delgado e grosso de 14 roedores foram examinados quanto à presença de helmintos. Três espécies de nematoides foram encontradas: Fuellebornema almeidai, Pterygodermatites (Paucipectines) sp. e Subulura forcipata. Considerando-se as três espécies, 85,7% dos roedores apresentaram pelo menos um helminto. F. almeidai foi a espécie mais prevalente, enquanto Subulura forcipata foi a mais abundante. Este estudo é o primeiro registro da estrutura da comunidade de helmintos para C. laticeps. Como resultado, foi registrado um novo hospedeiro e o aumento da área de distribuição geográfica para o nematódeo F. almeidai e o primeiro caso de Pterygodermatites (Paucipectines) sp. infectando um roedor equimídeo. Além disso, este estudo também traz o primeiro registro de S. forcipata infectando um mamífero.

Neglected Agent Eminent Disease: Linking Human Helminthic Infection, Inflammation, and Malignancy.

Helminthic parasitic infection is grossly prevalent across the globe and is considered a significant factor in human cancer occurrence induced by biological agents. Although only three helminths (Schistosoma haematobium, Clonorchis sinensis, and Opisthorchis viverrini) so far have been directly associated with carcinogenesis; there are evidence suggesting the involvement of other species too. Broadly, human helminthiasis can cause chronic inflammation, genetic instability, and host immune modulation by affecting inter- and intracellular communications, disruption of proliferation-anti-proliferation pathways, and stimulation of malignant stem cell progeny. These changes ultimately lead to tumor development through the secretion of soluble factors that interact with host cells. However, the detailed mechanisms by which helminths introduce and promote malignant transformation of host cells are still not clear. Here, we reviewed the current understanding of immune-pathogenesis of helminth parasites, which have been associated with carcinogenesis, and how these infections initiate carcinogenesis in the host.

Varying levels of melanotic encapsulation of gordiid hairworm cysts (Nematomorpha) by aquatic insect larvae: seasonal and host effects.

The defence reactions of insects to parasitic invaders are both varied and complex. Melanisation of pathogens is often an important step in insect immunity and can play a key role in isolating parasites. Within samples collected from a subalpine stream in New Zealand during two consecutive seasons (i.e., winter and spring), we observed and categorised different levels of melanotic encapsulation by aquatic insect larvae to dormant Gordius sp. hairworm (Phylum Nematomorpha) cysts, a relatively obscure group of parasites. Some of these insect species act as intermediate transport hosts in the complex life cycle of hairworms. Based on these new observations, we calculated the melanisation response for an abundant species of caddisfly larvae (Olinga sp.) using the proportion of non-melanised cysts per individual host. We tested the hypothesis that season and total number of cysts in an infected host impact its melanisation response. Also, we explored the effect of host body size on the total number of cysts it carries. We found that the total number of cysts does not affect the melanisation response of the host. Season did have an impact on the melanisation response in Olinga sp., with lower levels observed in the spring. Additionally, larger caddisfly larvae harboured more cysts than smaller ones. Since little is known about the cryptic interactions between hairworms and their intermediate hosts, this new information adds some complexity to this poorly understood group of parasites.

TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths.

Intestinal epithelial cells (IEC) have important functions in nutrient absorption, barrier integrity, regeneration, pathogen-sensing, and mucus secretion. Goblet cells are a specialized cell type of IEC that secrete Trefoil factor 3 (TFF3) to regulate mucus viscosity and wound healing, but whether TFF3-responsiveness requires a receptor is unclear. Here, we show that leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) is essential for TFF3-mediated functions. LINGO2 immunoprecipitates with TFF3, co-localizes with TFF3 on the cell membrane of IEC, and allows TFF3 to block apoptosis. We further show that TFF3-LINGO2 interactions disrupt EGFR-LINGO2 complexes resulting in enhanced EGFR signaling. Excessive basal EGFR activation in Lingo2 deficient mice increases disease severity during colitis and augments immunity against helminth infection. Conversely, TFF3 deficiency reduces helminth immunity. Thus, TFF3-LINGO2 interactions de-repress inhibitory LINGO2-EGFR complexes, allowing TFF3 to drive wound healing and immunity.

Macrophage Activation and Functions during Helminth Infection: Recent Advances from the Laboratory Mouse.

Macrophages are highly plastic innate immune cells that adopt an important diversity of phenotypes in response to environmental cues. Helminth infections induce strong type 2 cell-mediated immune responses, characterized among other things by production of high levels of interleukin- (IL-) 4 and IL-13. Alternative activation of macrophages by IL-4 in vitro was described as an opposite phenotype of classically activated macrophages, but the in vivo reality is much more complex. Their exact activation state as well as the role of these cells and associated molecules in type 2 immune responses remains to be fully understood. We can take advantage of a variety of helminth models available, each of which have their own feature including life cycle, site of infection, or pathological mechanisms influencing macrophage biology. Here, we reviewed the recent advances from the laboratory mouse about macrophage origin, polarization, activation, and effector functions during parasitic helminth infection.

Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.

Epithelial surfaces form critical barriers to the outside world and are continuously renewed by adult stem cells1. Whereas dynamics of epithelial stem cells during homeostasis are increasingly well understood, how stem cells are redirected from a tissue-maintenance program to initiate repair after injury remains unclear. Here we examined infection by Heligmosomoides polygyrus, a co-evolved pathosymbiont of mice, to assess the epithelial response to disruption of the mucosal barrier. H. polygyrus disrupts tissue integrity by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate2. Crypts overlying larvae-associated granulomas did not express intestinal stem cell markers, including Lgr53, in spite of continued epithelial proliferation. Granuloma-associated Lgr5- crypt epithelium activated an interferon-gamma (IFN-γ)-dependent transcriptional program, highlighted by Sca-1 expression, and IFN-γ-producing immune cells were found in granulomas. A similar epithelial response accompanied systemic activation of immune cells, intestinal irradiation, or ablation of Lgr5+ intestinal stem cells. When cultured in vitro, granuloma-associated crypt cells formed spheroids similar to those formed by fetal epithelium, and a sub-population of H. polygyrus-induced cells activated a fetal-like transcriptional program, demonstrating that adult intestinal tissues can repurpose aspects of fetal development. Therefore, re-initiation of the developmental program represents a fundamental mechanism by which the intestinal crypt can remodel itself to sustain function after injury.

Helminths of Dermatonotus muelleri (Anura: Microhylidae) from Northeastern Brazil.

The helminth fauna associated with Muller's termite frog, Dermatonotus muelleri, from the southern region of Ceará State, Brazil, was studied. The species richness was 6 helminth taxa, including cystacanths of Acanthocephala and 5 nematode species: Aplectana membranosa, Parapharyngodon silvoi, Raillietnema spectans, larvae of Physaloptera sp., and an unidentified nematode. The overall prevalence was 88.6%, with an average intensity of infection of 123.7 ± 26.3. The nematode Raillietnema spectans presented the highest prevalence and was the most abundant ( d = 0.670). Host body size did not influence the intensity of infection nor the richness of helminth species. This study increases the body of knowledge about the diversity of helminth fauna associated with Dermatonotus muelleri from northeastern Brazil, extending the record of hosts and the geographic distribution of these helminth species.

Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma.

During helminth infection and allergic asthma, naive CD4+ T-cells differentiate into cytokine-producing Type-2 helper (Th2) cells that resolve the infection or induce asthma-associated pathology. Mechanisms regulating the Th2 differentiation in vivo remain poorly understood. Here we report that mice lacking Bcl11b in mature T-cells have a diminished capacity to mount Th2 responses during helminth infection and allergic asthma, showing reduced Th2 cytokines and Gata3, and elevated Runx3. We provide evidence that Bcl11b is required to maintain chromatin accessibility at Th2-cytokine promoters and locus-control regions, and binds the Il4 HS IV silencer, reducing its accessibility. Bcl11b also binds Gata3-intronic and downstream-noncoding sites, sustaining the Gata3 expression. In addition, Bcl11b binds and deactivates upstream enhancers at Runx3 locus, restricting the Runx3 expression and its availability to act at the Il4 HS IV silencer. Thus, our results establish novel roles for Bcl11b in the regulatory loop that licenses Th2 program in vivo.

Helminth Infections: Recognition and Modulation of the Immune Response by Innate Immune Cells.

The survival of helminths in the host over long periods of time is the result of a process of adaptation or dynamic co-evolution between the host and the parasite. However, infection with helminth parasites causes damage to the host tissues producing the release of danger signals that induce the recruitment of various cells, including innate immune cells such as macrophages (Mo), dendritic cells (DCs), eosinophils, basophils, and mast cells. In this scenario, these cells are able to secrete soluble factors, which orchestrate immune effector mechanisms that depend on the different niches these parasites inhabit. Here, we focus on recent advances in the knowledge of excretory-secretory products (ESP), resulting from helminth recognition by DCs and Mo. Phagocytes and other cells types such as innate lymphocyte T cells 2 (ILC2), when activated by ESP, participate in an intricate cytokine network to generate innate and adaptive Th2 responses. In this review, we also discuss the mechanisms of innate immune cell-induced parasite killing and the tissue repair necessary to assure helminth survival over long periods of time.

Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across taxa.

A deeper understanding of the conserved molecular mechanisms in different taxa have been made possible only because of the evolutionary conservation of crucial signaling pathways. In the present study, we explored the molecular evolutionary pattern of selection signatures in 51 species for 10 genes which are important components of NAD+/Sirtuin pathway and have already been directly linked to lifespan extension in worms and mice. Selection pressure analysis using PAML program revealed that MRPS5 and PPARGC1A were under significant constraints because of their functional significance. FOXO3a also displayed strong purifying selection. All three sirtuins, which were SIRT1, SIRT2 and SIRT6, displayed a great degree of conservation between taxa, which is consistent with the previous report. A significant evolutionary constraint is seen on the anti-oxidant gene, SOD3. As expected, TP53 gene was under significant selection pressure in mammals, owing to its major role in tumor progression. Poly-ADP-ribose polymerase (PARP) genes displayed the most sites under positive selection. Further 3D structural analysis of PARP1 and PARP2 protein revealed that some of these positively selected sites caused a change in the electrostatic potential of the protein structure, which may allow a change in its interaction with other proteins and molecules ultimately leading to difference in the function. Although the functional significance of the positively selected sites could not be established in the variants databases, yet it will be interesting to see if these sites actually affect the function of PARP1 and PARP2.

Helminth-induced apoptosis: a silent strategy for immunosuppression.

During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling event evolved to cell death. It plays a pivotal role in several immunological reactions in particular deletion of autoreactive immune cells. Helminth-triggered apoptosis in immune cells exhausts host immunity, which paves the way for generating a permissive environment and chronic infection. This review provides a compilation of recent investigations discussing the apoptotic mechanisms exploited by different worms and the immunological consequences of immune cell death. Finally, the anti-cancer effects of some worm-derived molecules due to their apoptotic effects are discussed, highlighting as potentially druggable candidates to combat cancer.