Gastrointestinal helminth infection still constitutes a major public health issue, particularly in the developing world. As these parasites can undergo a large part of their lifecycle within the ...intestinal tract the host has developed various structural and cellular specializations at the epithelial barrier to contend with infection. Detailed characterization of these cells will provide important insights about their contributions to the protective responses mediated against helminths. Here, we discuss how key components of the intestinal epithelium may function to limit the initial establishment of helminths, and how these cells are altered during an active response to infection.
Previously, research on the mucosal immune response to gastrointestinal helminth infection has been limited by a lack of knowledge around defined subpopulations of intestinal epithelial cells (IECs) such as tuft cells and enteroendocrine cells.Recent advances in single-cell sequencing technology have allowed for more detailed identification of IEC subsets and their potential roles during helminth infection.The characterization of IEC subsets has led to advances in our knowledge of helminth–IEC interactions (e.g., tuft cell activation by helminths, which elicits a potent type 2 immune response).This review is a call to arms for the need to dissect the mechanisms as to how helminths initiate an immune response through these subsets, as well as the need to use modern sequencing technology to further characterize IEC subsets.
Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged ...as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology.
Type-2-cell-mediated immune responses play critical roles in regulating host resistance against helminths and promoting tissue repair and metabolic homeostasis. Harris and Loke review recent advances in the field resulting from studies of helminth-host interactions and provide insight into the activation and function of type 2 immune cells.
Intestinal helminths, along with mutualistic microbes, have cohabited the intestine of mammals throughout evolution. Interactions between helminths, bacteria, and their mammalian hosts may shape not ...only host–helminth and host–microbiome interactions, but also the relationship between helminths and the microbiome. This ‘ménage à trois’ situation may not be completely balanced in that it may favor either the host or the parasite, possibly at the cost of the other partner. Similarly, helminths may favor the establishment of a particular microbiome with either positive or negative consequences for the overall health and well-being of the host. Recent studies indicate that infection with intestinal helminths can and does impact the intestinal microbiome, with important consequences for each partner in this tripartite relationship.
In humans, both cross-sectional and case-control studies performed in regions endemic for intestinal helminths provided evidence that infection may alter fecal bacterial communities.
In mice, infection with the large intestinal helminth Trichuris muris can promote colonization resistance against the pathogenic bacterium Bacteroides vulgatus by promoting the growth of nonpathogenic bacterial species.
In mice, infection with the small intestinal helminth Heligmosomoides polygyrus has been shown to alter the cecal microbiome and results in greater availability of bacterially derived metabolites, SCFAs, that function to dampen allergic responses.
Intestinal helminths are potent regulators of their host’s immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this ...anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions.
•The microbiota contributes to helminth-induced modulation of allergic asthma•Cecal microbial communities are altered in helminth-infected mice•Helminth infection increases microbial-derived short chain fatty acids•GPR41 mediates helminth-induced Treg cell suppressor function
Intestinal helminths are well known to possess potent immunomodulatory capacities. Harris and colleagues demonstrate in mice that helminth infection alters the bacterial microbiota and increases the concentration of short chain fatty acids (SCFAs), which reduce allergic asthma via GPR41. Increased intestinal SCFA concentrations were conserved across multiple parasite and host species.
Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk ...influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.
The intestinal epithelium interacts with immune cells to support tissue homeostasis and coordinate responses against pathogens. In this issue of Immunity, Yang et al. unveil a central role for mast ...cell-epithelial cell interactions in orchestrating protective type 2 immune responses following intestinal helminth infection.
The intestinal epithelium interacts with immune cells to support tissue homeostasis and coordinate responses against pathogens. In this issue of Immunity, Yang et al. unveil a central role for mast cell-epithelial cell interactions in orchestrating protective type 2 immune responses following intestinal helminth infection.
Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues ...bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.
Just as mammals have coevolved with the intestinal bacterial communities that are part of the microbiota, intestinal helminths represent an important selective force on their mammalian host. The ...complex interaction between helminths, microbes, and their mammalian host is likely an important determinant of mutual fitness. The host immune system in particular is a critical interface with both helminths and the microbiota, and this crosstalk often determines the balance between tolerance and resistance against these widespread parasites. Hence, there are many examples of how both helminths and the microbiota can influence tissue homeostasis and homeostatic immunity. Understanding these processes at a cellular and molecular level is an exciting area of research that we seek to highlight in this review and that will potentially guide future treatment approaches.
Both the intestinal microbiota and helminths represent important selective forces on their mammalian hosts. Loke and Harris examine trans-kingdom interactions between the microbiota and helminths that occur across a large range of parasite and host species as well as their impacts on parasite fitness and host health and disease.
Adding data to gut feelings Marsland, Benjamin J; Harris, Nicola L
Cell,
10/2022, Letnik:
185, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Pain-sensing neurons detect environmental insults and tissue injury, driving avoidance behavior and the local release of neuropeptides. Two related papers in this issue of Cell report that ...gut-innervating pain neurons sense bacterial presence to both shape the constituents of the gut microbiome and protect against excessive inflammation.
Eosinophils are granulocytes, typically implicated as end-stage effector cells in type-II immune responses. They are capable of producing a wide array of pre-formed molecules which render them with ...vast potential to influence a wide variety of processes. Nonetheless, eosinophil research has traditionally focused on their role in anti-helminthic responses and pathophysiological processes in type-II immune disorders, such as allergy and asthma, where eosinophilia is a hallmark phenotype. However, a number of key studies over the past decade have placed this restricted view of eosinophil function into question, presenting additional evidence for eosinophils as critical regulators of various homeostatic processes including immune maintenance, organ development, and tissue regeneration.
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