Regulatory Immune Mechanisms in Tolerance to Food Allergy

Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments

The lack of L-PG production and the repercussions of it in regards to M. Tuberculosis interactions with mononuclear phagocytes

The lysine connection with phosphatidylglycerol (PG) alters the M. tuberculosis(Mtb) surface charge, and consequently it may decrease the bacterial vulnerability to antimicrobial action of the immune cells. The aim of the study was to assess the significance of PG lysinylation in the Mtb interactions with mononuclear phagocytes. Both the Mtb strain with deletion of lysX gene (Mtb-lysX) which is responsible for PG lysinylation as well as the complemented strain (Mtb-compl) was used to infect human blood monocytes or THP-1 cells. The monocytes were obtained by MACS technique, or THP-1 cells. The Mtb-lysX strain has exhibited the enhanced sensitivity to HNP 1-3. However, it was not susceptible to bactericidal action of cathepsin G. The LysX deletion did not influence the Mtb ability of monocyte induction to IL-10 secretion. The intra- and extracellular expression of MHC-II was similarly reduced after the Mtb-lysX or Mtb-Rv infections. Noticeably significant is that the Mtb strain with deleted lysX has not affected the intensity of the gene expression of cathepsin G compared to the uninfected monocytes. That is the clear contrast to what the Mtb-Rv strain has proved. The obtained results suggest that the Mtb ability to lysinylate PG is a participatory element in mycobacterial strategy of survival inside phagocytic cells. However, the extended studies are needed to determine its influence on the other immune cells and define its role in the developing of Mtb infection

Mechanisms of allergen-specific immunotherapy

Objective The aim of this review is to provide an overview of the current knowledge on the mechanisms of allergen immunotherapy based on the recent publications and clinical trials. Data sources PubMed literature review. Study selections In this review, we focus on diverse mechanisms of AIT and provide an insight into alternative routes of administration. Additionally, we review and discuss the most recent studies investigating potential biomarkers and highlight their role in clinical settings. Results Successful allergen-specific immunotherapy (AIT) induces the reinstatement of tolerance toward allergens and represents a disease-modifying treatment. In the last decades, substantial progress in understanding the mechanisms of AIT has been achieved. Establishment of long-term clinical tolerance to allergens engages a complex network of interactions, modulating the functions of basophils, mast cells, allergen-specific regulatory T and B cells, and production of specific antibodies. The reduction of symptoms and clinical improvement is achieved by skewing the immune response away from allergic inflammation. Conclusion Although the complex nature of AIT mechanisms is becoming more clear, the need to discover reliable biomarkers to define patients likely to respond to the treatment is emerging

Innate Immune Response to Viral Infections in Primary Bronchial Epithelial Cells is Modified by the Atopic Status of Asthmatic Patients

Purpose In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. Methods HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures. HBECs were infected with parainfluenza virus (PIV)-3 (MOI 0.1) and rhinovirus (RV)-1B (MOI 0.1), or treated with medium alone. The cell supernatants were harvested at 8, 24, and 48 hours. IFN-α, CXCL10 (IP-10), and RANTES (CCL5) were analyzed by using Cytometric Bead Array (CBA), and interferon (IFN)-β and IFN-λ1 by ELISA. Gene expression of IFNs, chemokines, and IFN-regulatory factors (IRF-3 and IRF-7) was determined by using quantitative PCR. Results PIV3 and RV1B infections increased IFN-λ1 mRNA expression in HBECs from asthmatics and healthy controls to a similar extent, and virus-induced IFN-λ1 expression correlated positively with IRF-7 expression. Following PIV3 infection, IP-10 protein release and mRNA expression were significantly higher in asthmatics compared to healthy controls (median 36.03-fold). No differences in the release or expression of RANTES, IFN-λ1 protein and mRNA, or IFN-α and IFN-β mRNA between asthmatics and healthy controls were observed. However, when asthmatics were divided according to their atopic status, HBECs from atopic asthmatics (n=6) generated significantly more IFN-λ1 protein and demonstrated higher IFN-α, IFN-β, and IRF-7 mRNA expressions in response to PIV3 compared to non-atopic asthmatics (n=4) and healthy controls (n=9). In response to RV1B infection, IFN-β mRNA expression was lower (12.39-fold at 24 hours and 19.37-fold at 48 hours) in non-atopic asthmatics compared to atopic asthmatics. Conclusions The immune response of HBECs to virus infections may not be deficient in asthmatics, but seems to be modified by atopic status. Keywords: Asthma; bronchial epithelial cells; interferon; parainfluenza virus; rhinoviru

Comparison of regulatory B cells in asthma and allergic rhinitis

International audienc

Modified Allergens for Immunotherapy

Purpose of Review During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. Recent Findings In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. Summary The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT. Keywords Allergen-specific immunotherapy COPs SPIREs Nanoparticles Allergoid