Snakes of the genus Bothrops inhabit tropical forests in Central and South America and are important for the biomedical and pharmaceutical industries because of the chemical properties of their venom. They serve as either definitive or intermediate hosts for many parasitic helminths. The Marajó Island (Brazil) is the natural habitat of venomous snakes, Bothrops atrox and Bothrops marajoensis, which are often found around rural and peri-urban areas and are known to bite humans. Samples of helminths parasitizing the oral cavity, subcutaneous tissues, coelomic cavity, and intestine of four B. atrox from Marajó Island (Pará-Brazil) were collected. The specimens studied were taxonomically classified as trematodes of the species Stycholecitha serpentis, nematodes of the genera Eustrongylides and Camallanus and cystacanths of an acanthocephalan of the genus Centrorhynchus. The aims of the present study were: to record helminths found in B. atrox from the Marajó Island; to discuss their role as definitive, intermediate, or paratenic hosts; and to compile a list of helminths that have been recorded in snakes of the genus Bothrops of the Neotropical region.

Two studies defined how tuft cell acetylcholine promotes parasite expulsion. Billip et al. demonstrated that acetylcholine increases water secretion, to promote the \'weep\' response. Ndjim et al. found that tuft cell acetylcholine has a direct effect on worm fecundity. Both processes are only effective in the remodeled epithelium when the rare tuft cells have become abundant.

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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.

UNASSIGNED: Protective immunity against intestinal helminths requires induction of robust type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation, and smooth muscle contractions to expel worms and re-establish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection, and inflammation. Macrophages are highly plastic cells that acquire an alternatively activated state during helminth infection, but they were previously shown to be dispensable for resistance to Trichuris muris infection.
UNASSIGNED: We use the in vivo mouse model A20myel-KO, characterized by the deletion of the potent anti-inflammatory factor A20 (TNFAIP3) specifically in the myeloid cells, the excessive type-1 cytokine production, and the development of spontaneous arthritis. We infect A20myel-KO mice with the gastrointestinal helminth Trichuris muris and we analyzed the innate and adaptive responses. We performed RNA sequencing on sorted myeloid cells to investigate the role of A20 on macrophage polarization and type-2 immunity. Moreover, we assess in A20myel-KO mice the pharmacological inhibition of type-1 cytokine pathways on helminth clearance and the infection with Salmonella typhimurium.
UNASSIGNED: We show that proper macrophage polarization is essential for helminth clearance, and we identify A20 as an essential myeloid factor for the induction of type-2 immune responses against Trichuris muris. A20myel-KO mice are characterized by persistent Trichuris muris infection and intestinal inflammation. Myeloid A20 deficiency induces strong classical macrophage polarization which impedes anti-helminth type-2 immune activation; however, it promotes detrimental Th1/Th17 responses. Antibody-mediated neutralization of the type-1 cytokines IFN-γ, IL-18, and IL-12 prevents myeloid-orchestrated Th1 polarization and re-establishes type-2-mediated protective immunity against T. muris in A20myel-KO mice. In contrast, the strong Th1-biased immunity in A20myel-KO mice offers protection against Salmonella typhimurium infection.
UNASSIGNED: We hereby identify A20 as a critical myeloid factor for correct macrophage polarization and appropriate adaptive mucosal immunity in response to helminth and enteric bacterial infection.

To determine the role that the IL-4/IL13 receptor plays in the development of alternatively activated macrophages (AAM or M2) and their role in the regulation of immunity to the extraintestinal phase of the helminth parasite Taenia crassiceps, we followed the infection in a mouse strain lacking the IL-4Rα gene (IL-4Rα-/-) and in the macrophage/neutrophil-specific IL-4Rα-deficient mouse strain (LysMcreIL-4Rα-/lox or cre/LoxP). While 100% of T. crassiceps-infected IL-4Rα+/+ (WT) mice harbored large parasite loads, more than 50% of th eIL-4Rα-/- mice resolved the infection. Approximately 88% of the LysMcreIL-4Rα-/lox mice displayed a sterilizing immunity to the infection. The remaining few infected cre/LoxP mice displayed the lowest number of larvae in their peritoneal cavity. The inability of the WT mice to control the infection was associated with antigen-specific Th2-type responses with higher levels of IgG1, IL-4, IL-13, and total IgE, reduced NO production, and increased arginase activity. In contrast, IL-4Rα-/- semi-resistant mice showed a Th1/Th2 combined response. Furthermore, macrophages from the WT mice displayed higher transcripts for Arginase-1 and RELM-α, as well as increased expression of PD-L2 with robust suppressive activity over anti-CD3/CD28 stimulated T cells; all of these features are associated with the AAM or M2 macrophage phenotype. In contrast, both the IL-4Rα-/- and LysMcreIL-4Rα-/lox mice did not fully develop AAM or display suppressive activity over CD3/CD28 stimulated T cells, reducing PDL2 expression. Additionally, T-CD8+ but no T-CD4+ cells showed a suppressive phenotype with increased Tim-3 and PD1 expression in WT and IL-4Rα-/-, which were absent in T. crassiceps-infected LysMcreIL-4Rα-/lox mice. These findings demonstrate a critical role for the IL-4 signaling pathway in sustaining AAM and its suppressive activity during cysticercosis, suggesting a pivotal role for AAM in favoring susceptibility to T. crassiceps infection. Thus, the absence of these suppressor cells is one of the leading mechanisms to control experimental cysticercosis successfully.

Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy.

OBJECTIVE: Vast majority of helminth diseases remain neglected tropical diseases (NTDs), causing significant morbidity. The widespread and periodic distribution of antiparasitic drugs, remains the cornerstone for controlling these diseases. In Spain, most helminthiasis cases are imported, and suspicion and diagnosis have become increasingly important. Our primary objective is to present the epidemiological landscape of helminthiasis diagnoses within our facility, while also detailing the demographic characteristics of the affected population.
METHODS: A retrospective study was conducted at the Hospital Universitario Severo Ochoa (HUSO) from January 1, 2007, to December 31, 2020, encompassing all diagnosed cases of helminthiasis during this period. Comprehensive epidemiological, clinical, and microbiological data were gathered for all diagnosed patients. The study population comprised patients receiving treatment at the HUSO, as well as those receiving treatment at the Leganés and Fuenlabrada Primary Care Units. Subsequently, descriptive and comparative statistics were performed, comparing Spanish and foreign patients.
RESULTS: During this period, a total of 952 patients were diagnosed with some form of helminthiasis. Among them, 495 were Spanish, and 457 were foreign. The total number of helminths identified, including patients with multiple infections, was 1,010. Significant differences were observed between Africans and Americans in terms of age distribution, with a higher prevalence among Africans in the 0-15 age range and among Americans in the 31-60 age range. Variations were noted in the distribution of helminths, with S. stercoralis significantly affecting Americans. For Spanish patients, the presence of Trichuris trichiura and S. stercoralis was significantly associated with eosinophilia, whereas among foreign patients, it was associated with Trichuris trichiura, Ascaris lumbricoides among others. Regarding symptoms, skin manifestations were more frequent among Spanish, while digestive were more common among foreigners.
CONCLUSIONS: This study offers crucial epidemiological insights into helminth infections observed over time in a Madrid hospital. Although the prevalence of helminth infections has been decreasing, there is still a need for screening and diagnosing foreign patients.

Energetic and nutritional requirements play a crucial role in shaping the immune cells that infiltrate tumor and parasite infection sites. The dynamic interaction between immune cells and the microenvironment, whether in the context of tumor or helminth infection, is essential for understanding the mechanisms of immunological polarization and developing strategies to manipulate them in order to promote a functional and efficient immune response that could aid in the treatment of these conditions. In this review, we present an overview of the immune response triggered during tumorigenesis and establishment of helminth infections, highlighting the transition to chronicity in both cases. We discuss the energetic demands of immune cells under normal conditions and in the presence of tumors and helminths. Additionally, we compare the metabolic changes that occur in the tumor microenvironment and the infection site, emphasizing the alterations that are induced to redirect the immune response, thereby promoting the survival of cancer cells or helminths. This emerging discipline provides valuable insights into disease pathogenesis. We also provide examples of novel strategies to enhance immune activity by targeting metabolic pathways that shape immune phenotypes, with the aim of achieving positive outcomes in cancer and helminth infections.

Amphiregulin (AREG) serves as a ligand for the epidermal growth factor receptor (EGFR) and is involved in vital biological functions, including inflammatory responses, tissue regeneration, and immune system function. Upon interaction with the EGFR, AREG initiates a series of signaling cascades necessary for several physiological activities, such as metabolism, cell cycle regulation, and cellular proliferation. Recent findings have provided evidence for the substantial role of AREG in maintaining the equilibrium of homeostasis in damaged tissues and preserving epithelial cell structure in the context of viral infections affecting the lungs. The development of resistance to influenza virus infection depends on the presence of type 1 cytokine responses. Following the eradication of the pathogen, the lungs are subsequently colonized by several cell types that are linked with type 2 immune responses. These cells contribute to the process of repairing and resolving the tissue injury and inflammation caused by infections. Following influenza infection, the activation of AREG promotes the regeneration of bronchial epithelial cells, enhancing the tissue\'s structural integrity and increasing the survival rate of infected mice. In the same manner, mice afflicted with influenza experience rapid mortality due to a subsequent bacterial infection in the pulmonary region when both bacterial and viral infections manifest concurrently inside the same host. The involvement of AREG in bacterial infections has been demonstrated. The gene AREG experiences increased transcriptional activity inside host cells in response to bacterial infections caused by pathogens such as Escherichia coli and Neisseria gonorrhea. In addition, AREG has been extensively studied as a mitogenic stimulus in epithelial cell layers. Consequently, it is regarded as a prospective contender that might potentially contribute to the observed epithelial cell reactions in helminth infection. Consistent with this finding, mice that lack the AREG gene exhibit a delay in the eradication of the intestinal parasite Trichuris muris. The observed delay is associated with a reduction in the proliferation rate of colonic epithelial cells compared to the infected animals in the control group. The aforementioned findings indicate that AREG plays a pivotal role in facilitating the activation of defensive mechanisms inside the epithelial cells of the intestinal tissue. The precise cellular sources of AREG in this specific context have not yet been determined. However, it is evident that the increased proliferation of the epithelial cell layer in infected mice is reliant on CD4+ T cells. The significance of this finding lies in its demonstration of the crucial role played by the interaction between immunological and epithelial cells in regulating the AREG-EGFR pathway. Additional research is necessary to delve into the cellular origins and signaling mechanisms that govern the synthesis of AREG and its tissue-protective properties, independent of infection.