Inflammasomes and dermatology

Abstract: Inflammasomes are intracellular multiprotein complexes that comprise part of the innate immune response. Since their definition, inflammasome disorders have been linked to an increasing number of diseases. Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). Concepts from other pathologies have also been reviewed in recent years, such as psoriasis, after the recognition of a combined contribution of innate and adaptive immunity in its pathogenesis. Inflammasomes are also involved in the response to various infections, malignancies, such as melanoma, autoimmune diseases, including vitiligo and lupus erythematosus, atopic and contact dermatitis, acne, hidradenitis suppurativa, among others. Inhibition of the inflammasome pathway may be a target for future therapies, as already occurs in the handling of CAPS, through the introduction of IL-1 inhibitors. This study presents a literature review focusing on the participation of inflammasomes in skin diseases.

NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

Role of Innate Immunity in the Pathogenesis of Type 1 and Type 2 Diabetes

The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.

NLRP3 Inflammasome and Host Protection against Bacterial Infection

The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.