Allergy, Asthma, and Inflammation: Which Inflammatory Cell Type Is More Important?

<p/> <p>A recent review in <it>Allergy, Asthma, and Clinical Immunology </it>suggested that eosinophils play a minor role, if any, in the inflammatory spectrum of asthma and allergic inflammation. The article that dealt with mast cells suggested that the presence of these important cells within the smooth muscle layer in asthmatic airways renders this cell type primal in asthma and an obvious and important target for therapy. This article proposes that in a complex inflammatory milieu characterizing the complex syndromes we call asthma, no single cell phenotype is responsible for the condition and thus should be a sole target for therapeutic strategies. Our reductionist approach to research in asthma and related conditions has provided us with convincing evidence for multiple roles that immune, inflammatory, and structural cell types can play in complex diseases. The next stage in understanding and ameliorating these complex conditions is to move away from the simplistic notion of one cell type being more important than another. Instead, what is needed is to acquire knowledge of intricate and exquisite biological systems that regulate such conditions in both health and disease involving various cell types, mediators, pharmacologically active products, their multifaceted capacities, and their socio-biological networking.</p

Identification of a Ruminant Origin Group B Rotavirus Associated with Diarrhea Outbreaks in Foals

Equine rotavirus group A (ERVA) is one of the most common causes of foal diarrhea. Starting in February 2021, there was an increase in the frequency of severe watery to hemorrhagic diarrhea cases in neonatal foals in Central Kentucky. Diagnostic investigation of fecal samples failed to detect evidence of diarrhea-causing pathogens including ERVA. Based on Illumina-based metagenomic sequencing, we identified a novel equine rotavirus group B (ERVB) in fecal specimens from the affected foals in the absence of any other known enteric pathogens. Interestingly, the protein sequence of all 11 segments had greater than 96% identity with group B rotaviruses previously found in ruminants. Furthermore, phylogenetic analysis demonstrated clustering of the ERVB with group B rotaviruses of caprine and bovine strains from the USA. Subsequent analysis of 33 foal diarrheic samples by RT-qPCR identified 23 rotavirus B-positive cases (69.69%). These observations suggest that the ERVB originated from ruminants and was associated with outbreaks of neonatal foal diarrhea in the 2021 foaling season in Kentucky. Emergence of the ruminant-like group B rotavirus in foals clearly warrants further investigation due to the significant impact of the disease in neonatal foals and its economic impact on the equine industry

Innate immune response to double-stranded RNA in American heritage chicken breeds

ABSTRACT: Backyard poultry flocks that employ heritage breeds of chicken play a crucial role in the maintenance of poultry pathogens of economic and zoonotic importance. This study examined innate immunity to viral pathogens in heritage chicken breeds using a model of viral double-stranded RNA (dsRNA). Following intraperitoneal injection of high molecular weight (HMW) -poly(I:C)/Lyovec into 4-wk-old chicks, we evaluated gene expression in peripheral blood mononuclear cells (PBMCs) and splenocytes. There was a significant difference across breeds in the expression of IL-4, IL-12p40, IFNγ, and B-cell activating factor (BAFF) in the spleen. In PBMCs, a significant difference in IFN-α expression was seen across breeds. Approximately 57% of IFN-α transcripts in PBMCs was explained by levels of expression of MDA5 transcripts. Using flow cytometry, we showed that only monocytes/macrophages (KUL01+ cells) expressed the scavenger receptor CD163. Regression analysis showed that 42% of fold change in CD163 expression on PBMCs was explained by breed (P < 0.0004). In general, breeds that responded to HMW-poly(I:C) by showing higher upregulation of IFNγ, IL-1β, and IL-12p40 transcripts in the spleen, and higher IFNα transcripts in peripheral blood, expressed less CD163 on blood monocytes. These findings suggest a genetic basis for the response of chickens to double-stranded RNA. Surface expression of the scavenger receptor CD163 in PBMCs following injection of high molecular weight poly(I:C) may be a rapid method to select chickens for breeding based on innate immune response to viral dsRNA

Thymic Indoleamine 2,3-Dioxygenase-Positive Eosinophils in Young Children : Potential Role In Maturation of the Naive Immune System

Eosinophils expressing indoleamine 2, 3-dioxygenase (IDO) may contribute to T-helper cell (Th)2 predominance. To characterize human thymus IDO+ eosinophil ontogeny relative to Th2 regulatory gene expression, we processed surgically obtained thymi from 22 children (age: 7 days to 12 years) for immunohistochemistry and molecular analysis, and measured cytokine and kynurenine levels in tissue homogenates. Luna+ eosinophils (∼2% of total thymic cells) decreased in number with age (P = 0.02) and were IDO+. Thymic IDO immunoreactivity (P = 0.01) and kynurenine concentration (P = 0.01) decreased with age as well. In addition, constitutively-expressed interleukin (IL)-5 and IL-13 in thymus supernatants was highest in youngest children. Eosinophil numbers correlated positively with expression of the Th2 cytokines IL-5, IL-13 (r = 0.44, P = 0.002), and IL-4 (r = 0.46, P = 0.005), transcription factor signal transducer and activator of transcription-6 (r = 0.68, P = 0.001), and the chemokine receptor, CCR3 (r = 0.17, P = 0.04), but negatively with IL-17 mRNA (r = −0.57, P = 0.02) and toll-like receptor 4 expression (r = −0.74, P = 0.002). Taken together, these results suggest that functional thymic IDO+ eosinophils during human infant life may have an immunomodulatory role in Th2 immune responses

Emerging concepts

My attraction to science and doing basic research comes from the misguided perspective, which usually develops early in life, that the world and events can be described from first principles. One simply had to devise ways to explain the series of absolute truths that surround us—the sky is blue, water is wet, and eosinophils are clearly the most important leukocytes in the blood (sorry … I simply couldn’t help myself!). Unfortunately, too many of us never fully lose this simplistic early childhood view of the world and it interferes with our thinking as we try to develop hypotheses to account for experimental observations. That is, the eosinophil community at large (including me!) is often not immune to this bias. Many times the only eosinophil studies believed are the ones that reinforce previously held views and fundable research is usually only an incremental advance on previously established results. While this cynical view of the eosinophil research is clearly an exaggeration, sadly, there are more elements of truth here than most of us are willing to admit in public. On this point, the enduring and pervasive character of this safe and intellectually soft approach is surprisingly robust. This is especially true given the truly extraordinary scientific achievements in biomedical science that have occurred from thinking outside the box. One need look no further than the story surrounding the molecular tools that are now indispensable and commonplace elements of research activities in any medical center. Who would have thought that studies of bacterial mating types and host defense strategies against bacterial phages (see for example) could possibly have led to the molecular biology revolution that is the driving force currently behind many basic as well as patient-based clinical studies. Even in those cases where the ideas and concepts were eventually refuted, the resulting discussions and debates substantially move areas of research forward. For example, in 1969 Britten and Davidson proposed a model for eukaryotic gene expression based on the presence of repetitive elements that could regulate batteries of genes in a coordinated fashion. Clearly, subsequent studies showed the shortcomings of this hypothesis. Nonetheless, the outside-the-box character of this idea created the discourse and experimental strategies that have led to the currently accepted understanding of unique cis-acting regulatory sequence elements that drive the coordinated expression of multiple genes and/or gene families. I would suggest that this type of event (i.e., thinking outside the confines of established parameters) isn’t an oddity at all and is instead all too often a moment of clarity. In this spirit, the coauthors of the subchapters within this ‘Emerging Concepts’ chapter describe research that neither reinforces current views of eosinophil effector functions nor are incremental advances of existing paradigms. As the heading suggests, you never know where the next ideas will come from or how far they will take you