The coronavirus disease 2019 (COVID-19) pandemic cost 7–8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in acute respiratory distress syndrome (ARDS) and lung injury. Anti-inflammatory intervention with anti-interleukin-6 (anti-IL-6) receptor monoclonal antibodies (mAbs; e.g., sarilumab and tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and/or steroid-based approach leads to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this review, the authors have summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus-host immune cross talks and presenting the possibilities of therapeutic intervention.

Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients.

Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ.

Autoimmune and autoinflammatory diseases affecting the inner ear can cause symptoms such as hearing loss, imbalance, vertigo, and tinnitus, presenting demanding and often underdiagnosed conditions. Diagnostic challenges arise due to their diverse manifestations, potential long-term consequences, and the absence of specific serological markers, necessitating a multidisciplinary approach combining clinical evaluation, audiological assessments, and imaging techniques. Various autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, have been implicated in immune-mediated damage to auditory structures, resulting in inner ear dysfunction. Inflammatory processes in autoinflammatory diseases like Cogan’s syndrome and relapsing polychondritis can also affect the inner ear. While the exact mechanisms of inner ear involvement in these conditions are still being studied, immune-mediated inflammation, damage to auditory structures, and vascular involvement play significant roles in auditory impairments. Treatment strategies primarily focus on immunomodulation and inflammation control using corticosteroids, immunosuppressants, and targeted biologic agents to ameliorate symptoms and preserve hearing function. Hearing aids and cochlear implants may be also considered for severe hearing loss. Individualized approaches are necessary due to patient response heterogeneity. This review provides a concise overview of key autoimmune and autoinflammatory diseases impacting the inner ear, highlighting clinical manifestations, diagnostics, pathophysiology, and treatment options. Early recognition and appropriate management are crucial for optimizing patient outcomes. Further research is needed to understand underlying mechanisms and identify novel therapeutic targets. Collaboration between otolaryngologists, rheumatologists, and immunologists is crucial for improving the quality of life in these complex conditions.

The intestinal mucosal barrier plays a critical role in maintaining the integrity of the gastrointestinal (GI) tract and protecting the body from harmful toxins and pathogens. Nutrition additionally serves as a vital component in maintaining bodily homeostasis. Macronutrients, micronutrients, and specific dietary habits exert profound effects on the immune system. The complex interactions of the immune system reflect a multifaceted, integrated epithelial and immune cell-mediated regulatory system. While several factors can influence the intestinal mucosal barrier and its pro- and anti-inflammatory processes, such as myeloid cell, regulatory T cell (Treg), or intraepithelial lymphocyte populations, there is growing evidence that macronutrients play an essential role in regulating its function. Herein this is a review of the peer-reviewed literature pertaining to dietary effects on mucosal integrity, including intraepithelial lymphocyte populations and immune function. This review is intended to explore the underlying mechanisms by which macronutrients impact and modulate the mucosal immune system.

Epididymitis or epididymo-orchitis is a common urological condition in males characterized by scrotal pain, swelling, and potential urinary symptoms. Although antibiotics can eliminate the causative pathogens, persistent inflammation may compromise spermatogenesis and steroidogenesis. The testis, an immune-privileged organ, possesses a specialized immune microenvironment that shields germ cells (GCs) from autoimmune attacks and orchestrates immune defenses against pathogens. This review focuses on the complex interplay between immune cells, including macrophages, dendritic cells (DCs), mast cells (MCs), and T cell subsets, in the testis. The roles of these immune cells in infection-induced orchitis were deliberated upon, emphasizing their involvement in inflammation and immune tolerance. Furthermore, the implications of testicular fibrosis and its effect on male infertility are discussed, emphasizing the role of MCs in tissue remodeling. The objective of this review is to expand comprehension of male reproductive health and foster the identification of potential therapeutic targets for epididymo-orchitis.

Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders-multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets.

Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed.

Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) ( n = 6), longitudinal extensive transverse myelitis (LETM) ( n = 2), multifocal spinal cord lesions ( n = 1), and myelitis involving dorsal and lateral columns ( n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability.

Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied.

Periodontitis is a ubiquitous chronic inflammatory worldwide disease. The multiplicity of gram-negative microbiomes and their endotoxins, such as lipopolysaccharides (LPS), play a crucial role in its pathogenesis. The detection and consequent effects of LPS occur either via membrane-based cluster of differentiation 14 (CD14)/myeloid differentiation factor 2 (MD2)/Toll-like receptor (TLR)-4 complex activation or through intracellular cytosolic LPS detection that further cascades its effects, resulting in a variety of cell death processes, including apoptosis, pyroptosis, necroptosis, NETosis, and their crosstalk. Irrespective of the detection of LPS, the cellular response is for protecting and resolving the inflammation. However, chronic and exaggerated responses in periodontitis result in the destruction of periodontal structures. This review summarizes the extracellular and cytosolic detection of LPS and its further consequences. Then, it sheds light on methods reported to mitigate the adverse effects of LPS.