HLA-DR regulatory T cells and IL-10 are associated with success or failure of desensitization outcomes.

Background: Omalizumab (XOLAIR®)-assisted multi-food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab-assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab-assisted mOIT and desensitization outcomes has not yet been fully elucidated.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

Background: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined.

Methods: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors.

A novel mass cytometry protocol optimized for immunophenotyping of low-frequency antigen-specific T cells.

Understanding antigen-specific T-cell responses, for example, following virus infections or allergen exposure, is of high relevance for the development of vaccines and therapeutics. We aimed on optimizing immunophenotyping of T cells after antigen stimulation by improving staining procedures for flow and mass cytometry. Our method can be used for primary cells of both mouse and human origin for the detection of low-frequency T-cell response using a dual-barcoding system for individual samples and conditions.

Combining avidin with CD63 improves basophil activation test accuracy in classifying peanut allergy.

Background: Conventional basophil activation tests (BATs) measure basophil activation by the increased expression of CD63. Previously, fluorophore-labeled avidin, a positively-charged molecule, was found to bind to activated basophils, which tend to expose negatively charged granule constituents during degranulation. This study further compares avidin versus CD63 as basophil activation biomarkers in classifying peanut allergy.

Proinflammatory polarization of monocytes by particulate air pollutants is mediated by induction of trained immunity in pediatric asthma.

Background: The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM ) are associated with alterations in circulating monocytes in children with or without asthma.

CD8 T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy.

While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs.

Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8 T cells in the draining lymph nodes are the major producers of this circulating IFN-γ.

Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System.

Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.

Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.

CyAnno: a semi-automated approach for cell type annotation of mass cytometry datasets.

Motivation: For immune system monitoring in large-scale studies at the single-cell resolution using CyTOF, (semi-)automated computational methods are applied for annotating live cells of mixed cell types. Here, we show that the live cell pool can be highly enriched with undefined heterogeneous cells, i.e.

Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab.

Background: Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.

Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8, and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life.

IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life.

Allergen-specific CD8 T cells in peanut-allergic individuals.

CD8 T cells are seldom considered in IgE mediated food allergy; we show that peanut specific CD8 T cells are increased in peanut allergic human subjects.

Tomato receptor FLAGELLIN-SENSING 3 binds flgII-28 and activates the plant immune system.

Plants and animals detect the presence of potential pathogens through the perception of conserved microbial patterns by cell surface receptors. Certain solanaceous plants, including tomato, potato and pepper, detect flgII-28, a region of bacterial flagellin that is distinct from that perceived by the well-characterized FLAGELLIN-SENSING 2 receptor. Here we identify and characterize the receptor responsible for this recognition in tomato, called FLAGELLIN-SENSING 3.

A novel method of transcriptome interpretation reveals a quantitative suppressive effect on tomato immune signaling by two domains in a single pathogen effector protein.

Background: Effector proteins are translocated into host cells by plant-pathogens to undermine pattern-triggered immunity (PTI), the plant response to microbe-associated molecular patterns that interferes with the infection process. Individual effectors are found in variable repertoires where some constituents target the same pathways. The effector protein AvrPto from Pseudomonas syringae has a core domain (CD) and C-terminal domain (CTD) that each promotes bacterial growth and virulence in tomato.

Identification of a Candidate Gene in Solanum habrochaites for Resistance to a Race 1 Strain of Pseudomonas syringae pv. tomato.

Bacterial speck disease caused by Pseudomonas syringae pv. tomato (Pst) is a persistent problem on tomato (Solanum lycopersicum L.).

Transcriptomic analysis reveals tomato genes whose expression is induced specifically during effector-triggered immunity and identifies the Epk1 protein kinase which is required for the host response to three bacterial effector proteins.

Background: Plants have two related immune systems to defend themselves against pathogen attack. Initially,pattern-triggered immunity is activated upon recognition of microbe-associated molecular patterns by pattern recognition receptors. Pathogenic bacteria deliver effector proteins into the plant cell that interfere with this immune response and promote disease.

Natural variation for responsiveness to flg22, flgII-28, and csp22 and Pseudomonas syringae pv. tomato in heirloom tomatoes.

Tomato (Solanum lycopersicum L.) is susceptible to many diseases including bacterial speck caused by Pseudomonas syringae pv. tomato.