Mast Cells Respond to Cell Injury through the Recognition of IL-33

Mast cells have been attributed several functions in both health and disease. Mast cell activation and release of inflammatory mediators are associated with the pathogenesis of several diseases, in particular that of allergic diseases. While the notion of mast cells as important, protective sentinel cells is old, this feature of the cell is not well recognized outside the mast cell field. The mast cell is a unique, multifunctional cell of our defense system, with characteristics such as wide-spread tissue distribution, expression of receptors capable of recognizing both endogenous and exogenous agents, and a capability to rapidly respond to triggering factors by selective mediator release. In this review, we discuss the function of mast cells as sentinel cells in the context of cell injury, where mast cells respond by initiating an inflammatory response. In this setting, IL-33 has turned out to be of particular interest. IL-33 is released by necrotic structural cells and is recognized by mast cells via the IL-33 receptor ST2. IL-33 and mast cells probably constitute one important link between cell injury and an inflammatory response that can lead to restoration of tissue function and homeostasis, but might under other circumstances contribute to a vicious circle driving chronic inflammation

Host protective roles of type 2 immunity:Parasite killing and tissue repair, flip sides of the same coin

AbstractMetazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Type 2 immunity also protects the host against damage mediated by these large extracellular parasites as they migrate through the body. At the center of both the innate and adaptive type 2 immune response, is the IL-4Rα that mediates many of the key effector functions. Here we highlight the striking overlap between the molecules, cells and pathways that mediate both parasite control and tissue repair. We have proposed that adaptive Th2 immunity evolved out of our innate repair pathways to mediate both accelerated repair and parasite control in the face of continual assault from multicellular pathogens. Type 2 cytokines are involved in many aspects of mammalian physiology independent of helminth infection. Therefore understanding the evolutionary relationship between helminth killing and tissue repair should provide new insight into immune mechanisms of tissue protection in the face of physical injury

The Matrix-M™ adjuvant: A critical component of vaccines for the 21st century

Matrix-M™ adjuvant is a key component of several novel vaccine candidates. The Matrix-M adjuvant consists of two distinct fractions of saponins purified from the Quillaja saponaria Molina tree, combined with cholesterol and phospholipids to form 40-nm open cage-like nanoparticles, achieving potent adjuvanticity with a favorable safety profile. Matrix-M induces early activation of innate immune cells at the injection site and in the draining lymph nodes. This translates into improved magnitude and quality of the antibody response to the antigen, broadened epitope recognition, and the induction of a Th1-dominant immune response. Matrix-M-adjuvanted vaccines have a favorable safety profile and are well tolerated in clinical trials. In this review, we discuss the latest findings on the mechanisms of action, efficacy, and safety of Matrix-M adjuvant and other saponin-based adjuvants, with a focus on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine candidate NVX-CoV2373 developed to prevent coronavirus disease 2019 (COVID-19)