Search

Summary: Type 2 immune responses are most commonly associated with allergy and helminth parasite infections. Since the discovery of Th1 and Th2 immune responses more than 30 years ago, models of both allergic disease and helminth infections have been useful in characterizing the development, effector mechanisms and pathological consequences of type 2 immune responses. The observation that some helminth infections negatively correlate with allergic and inflammatory disease led to a large field of research into parasite immunomodulation. However, it is worth noting that helminth parasites are not always benign infections, and that helminth immunomodulation can have stimulatory as well as suppressive effects on allergic responses. In this review, we will discuss how parasitic infections change host responses, the consequences for bystander immunity and how this interaction influences clinical symptoms of allergy. [ABSTRACT FROM AUTHOR]

B-cells play a critical role in the formation of immune responses against pathogens by acting as antigen-presenting cells, by modulating immune responses and by generating immune memory and antibody responses. Here, we studied B-cell subset distributions between regions with higher and lower microbial exposure, i.e. by comparing peripheral blood B-cells from people living in Indonesia or Ghana to those from healthy Dutch residents using a 36-marker mass cytometry panel. By applying an unbiased multidimensional approach, we observed differences in the balance between the naïve and memory compartments, with higher CD11c+ and double negative (DN-IgDnegCD27neg) memory (M)B-cells in individuals from rural tropical areas, and conversely lower naïve B-cells compared to residents from an area with less pathogen exposure. Furthermore, characterization of total B-cell populations, CD11c+, DN and Breg cells showed the emergence of specific memory clusters in individuals living in rural tropical areas. Some of these differences were more pronounced in children compared to adults and suggest that a higher microbial exposure accelerates memory B cell formation, which 'normalizes' with age., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs), which constitute key components in the recognition of pathogens, thereby initiating innate immune responses and promoting adaptive immune responses. In B cells, TLR ligation is important for their activation and, together with CD40, for their differentiation. TLR ligands are also strong promoters of regulatory B (Breg)-cell development, by enhancing the production of IL-10 and their capacity to induce tolerance. In inflammatory diseases, such as autoimmunity or allergies, Breg-cell function is often impaired, while in chronic infections, such as with helminths, or cancer, Breg-cell function is boosted. Following pathogen exposure, B cells can respond directly by producing cytokines and/or IgM (innate response) and develop into various memory B (Bmem)-cell subsets with class-switched immunoglobulin receptors. Depending on the disease state or chronic infection conditions, various Breg subsets can be recognized as well. Currently, a large array of surface markers is known to distinguish between these large range of B-cell subsets. In recent years, the development of mass cytometers and spectral flow cytometry has allowed for high-dimensional detection of up to 48 markers, including both surface and intracellular/intranuclear markers. Therefore, this novel technology is highly suitable to provide a comprehensive overview of Bmem/Breg-cell subsets in different disease states and/or in clinical intervention trials. Here, we provide detailed instructions of the steps necessary to obtain high-quality data for high-dimensional analysis of multiple human Breg-cell subsets using various TLR ligands.