The intestine is a powerful digestive system and one of the most sophisticated immunological organs. Evidence shows that tuft cells (TCs), a kind of epithelial cell with distinct morphological characteristics, play a significant role in various physiological processes. TCs can be broadly categorized into different subtypes depending on different molecular criteria. In this review, we discuss its biological properties and role in maintaining homeostasis in the gastrointestinal tract. We also emphasize its relevance to the immune system and highlight its powerful influence on intestinal diseases, including inflammations and tumors. In addition, we provide fresh insights into future clinical diagnostic and therapeutic strategies related to TCs.

Vaccines are one of the most successful medical inventions to enable the eradication or control of common and fatal diseases. Environmental exposure of hosts, including helminth infections, plays an important role in immune responses to vaccines. Given that helminth infections are among the most common infectious diseases in the world, evaluating vaccine efficiency in helminth-infected populations may provide critical information for selecting optimal vaccination programs. Here, we reviewed the effects of helminth infections on vaccination and its underlying immunological mechanisms, based on findings from human studies and animal models. Moreover, the potential influence of helminth infections on SARS-CoV-2 vaccine was also discussed. Based on these findings, there is an urgent need for anthelmintic treatments to eliminate helminth suppressive impacts on vaccination effectiveness during implementing mass vaccination in parasite endemic areas.

Non-alcoholic fatty liver disease (NAFLD) is closely related to obesity, diabetes, and metabolic syndrome (MetS), and it has become the most common chronic liver disease. Helminths have co-evolved with humans, inducing multiple immunomodulatory mechanisms to modulate the host\'s immune system. By using their immunomodulatory ability, helminths and their products exhibit protection against various autoimmune and inflammatory diseases, including obesity, diabetes, and MetS, which are closely associated with NAFLD. Here, we review the pathogenesis of NAFLD from abnormal glycolipid metabolism, inflammation, and gut dysbiosis. Correspondingly, helminths and their products can treat or relieve these NAFLD-related diseases, including obesity, diabetes, and MetS, by promoting glycolipid metabolism homeostasis, regulating inflammation, and restoring the balance of gut microbiota. Considering that a large number of clinical trials have been carried out on helminths and their products for the treatment of inflammatory diseases with promising results, the treatment of NAFLD and obesity-related diseases by helminths is also a novel direction and strategy.

Type 2 immunity can be modulated by regulatory T (Treg) cell activity. It has been suggested that the deubiquitinase cylindromatosis (CYLD) plays a role in the development or function of Treg cells, implying that it could be important for normal protective immunity, where type 2 responses are prevalent.
We sought to investigate the role of CYLD in Treg cell function and TH2 cell immune responses under steady-state conditions and during helminth infection.
Foxp3-restricted CYLD conditional knockout (KO) mice were examined in mouse models of allergen-induced airway inflammation and Nippostrongylus brasiliensis infection. We performed multiplex magnetic bead assays, flow cytometry, and quantitative PCR to understand how a lack of CYLD affected cytokine production, homing, and suppression in Treg cells. Target genes regulated by CYLD were identified and validated by microarray analysis, coimmunoprecipitation, short hairpin RNA knockdown, and transfection assays.
Treg cell-specific CYLD KO mice showed severe spontaneous pulmonary inflammation with increased migration of Treg cells into the lung. CYLD-deficient Treg cells furthermore produced high levels of IL-4 and failed to suppress allergen-induced lung inflammation. Supporting this, the conditional KO mice displayed enhanced protection against N brasiliensis infection by contributing to type 2 immunity. Treg cell conversion into IL-4-producing cells was due to augmented mitogen-activated protein kinase and nuclear factor κB signaling. Moreover, Scinderin, a member of the actin-binding gelsolin family, was highly upregulated in CYLD-deficient Treg cells, and controlled IL-4 production through forming complexes with mitogen-activated protein kinase kinase/extracellular receptor kinase. Correspondingly, both excessive IL-4 production in vivo and the protective role of CYLD-deficient Treg cells against N brasiliensis were reversed by Scinderin ablation.
Our findings indicate that CYLD controls type 2 immune responses by regulating Treg cell conversion into TH2 cell-like effector cells, which potentiates parasite resistance.

The gut microbiota has been demonstrated to associate with protection against helminth infection and mediate via microbial effects on the host humoral immunity. As a non-permissive host of Schistosoma japonicum, the Microtus fortis provides an ideal animal model to be investigated, because of its natural self-healing capability. Although researches on the systemic immunological responses have revealed that the host immune system contributes a lot to the resistance, the role of gut microbiome remains unclear. In this study, we exposed the M. fortis to the S.japonicum infection, carried out a longitudinal research (uninfected control, infected for 7 days, 14 days, 21 days, and 31 days) on their colonic microbiota based on the 16S rRNA gene amplicon sequencing. The bacterial composition disclosed a disturbance-recovery alteration followed by the resistance to S. japonicum. The alpha diversity of colon microbiota was reduced after the infection, but it gradually recovered along with self-healing process. Further LEfSe analysis revealed that phyla shifted from Firmicutes to Bacteroidetes, which were mainly driven by an increase of Ruminococcaceae and a depletion of Muribaculaceae in the family level along the Control-Infection-Recovery (CIR) process. We identified a temporary blooming of Lactobacillaceae and Lactobacillus in the mid infection stage (D14). As a recognized probiotics repository, we speculate the increased abundance of Lactobacillaceae in M. fortis colonic microbiota might relate to the natural resistance to the schistosome. Besides, potential microbial functions were also significantly changed in the resistance process. These results demonstrate the remarkable alterations of reed vole colonic microbiota in both community structure and potential functions along with the resistance to S. japonicum infection. The identified microbial biomarkers might offer new ways for drug development to conquer human schistosomiasis.

Global health has substantially improved over the past 20 years. In low- and middle-income countries, in particular, great strives have been made in the control of communicable diseases, including helminth infections. Nevertheless, the most marginalised communities still suffer from infectious diseases that are intimately connected with poverty and lack of access to essential commodities and services, such as clean water, improved sanitation and sufficient food. A two-pronged approach is thus necessary: (i) intensifying control in remaining high-endemicity areas and pockets of high transmission; and (ii) moving from morbidity control to interruption of disease transmission in low-endemicity areas with the goal of local elimination. The latter will require new tools and strategies, going hand-in-hand with strong partnerships and new strategic alliances. In this special issue of Acta Tropica, 35 articles are featured that, together, provide an up-to-date overview of the latest progress made in research, control and elimination of helminth infections in East and Southeast Asia. The first 12 articles expound tools and approaches for improved detection, surveillance and monitoring of helminth infections. Control and elimination approaches for the most important helminth infections are revisited in the next 20 articles. The three remaining articles are cross-cutting pieces examining the interface of agriculture, environment and helminth infections and providing a rationale for integrated, multi-sectorial control approaches that are necessary for sustaining helminthiasis control and progressively moving towards elimination. An interesting aspect revealed through an in-depth analysis of the provenance of the 35 contributions is that the People\'s Republic of China emerges as a key player in global health, which is documented through its prominent role in research and control of helminth infection and networking throughout Asia. Policy implications are discussed and will hopefully shape the future agenda for the control and elimination of helminth infections the world over.