Experimental Allergy Models Research Articles

Basophils Orchestrating Eosinophils' Chemotaxis and Function in Allergic Inflammation.

Eosinophils are well known to contribute significantly to Th2 immunity, such as allergic inflammations. Although basophils have often not been considered in the pathogenicity of allergic dermatitis and asthma, their role in Th2 immunity has become apparent in recent years. Eosinophils and basophils are present at sites of allergic inflammations. It is therefore reasonable to speculate that these two types of granulocytes interact in vivo. In various experimental allergy models, basophils and eosinophils appear to be closely linked by directly or indirectly influencing each other since they are responsive to similar cytokines and chemokines. Indeed, basophils are shown to be the gatekeepers that are capable of regulating eosinophil entry into inflammatory tissue sites through activation-induced interactions with endothelium. However, the direct evidence that eosinophils and basophils interact is still rarely described. Nevertheless, new findings on the regulation and function of eosinophils and basophils biology reported in the last 25 years have shed some light on their potential interaction. This review will focus on the current knowledge that basophils may regulate the biology of eosinophil in atopic dermatitis and allergic asthma.

Elevated caspase‑1 activity and IL‑1β expression are associated with the IPAF inflammasome in an experimental model of allergy.

Previous studies have indicated that interleukin (IL)‑1β has an important role in the development of allergic diseases. Therefore, the present study aimed to investigate the upstream pathway underlying IL‑1β production in an experimental model of allergy. BALB/c mice (female, 6‑8 weeks old) were sensitized to recombinant (r)Che a 2 by intraperitoneal injection of rChe a 2 adsorbed onto an alum gel suspension on days 0, 7, 14 and 21. In the control group, mice received an injection of 20 mM phosphate‑buffered saline absorbed onto alum via the same route. The allergic status of the mice was confirmed serologically by measuring allergen‑specific immunoglobulin (Ig)E levels. The protein expression levels of IL‑1β and the mRNA expression levels of inflammasome compartments were measured by enzyme‑linked immunosorbent assay and semi‑quantitative reverse transcription polymerase chain reaction, respectively. In addition, caspase‑1 activity was determined by fluorometric assay. Sensitized mice exhibited significantly increased levels of specific IgE (P<0.05). IL‑1β production and caspase‑1 activity were significantly higher in the sensitized mice compared with the control group. In addition, no significant differences were observed between the control and sensitized mice in the expression of genes associated with the inflammasome, including NLR family, pyrin domain containing 3; apoptosis‑associated speck‑like protein; and NLR family, apoptosis inhibitory protein 5. However, IL‑1β converting enzyme protease‑activating factor (IPAF) expression was significantly increased in sensitized mice compared with in the control group (P<0.05). These data indicate that caspase‑1 activation and IL‑1β expression are associated with the IPAF inflammasome. Therefore, based on this association, the IPAF inflammasome may be considered for IL‑1β production in the experimental model of allergy.

Colonization by Superantigen Producing &amp;lt;i&amp;gt;Staphylococcus aureus&amp;lt;/i&amp;gt; in Mice Enhances the Capacity to Develop Oral Tolerance

Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protection in experimental allergy models. Here, we used three wild-type strains of S. aureus, naturally harboring genes for different superantigens (SElM/SElO alone, or in combination with SEA or TSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-free mice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oral tolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promoted the strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportion of CD4+FoxP3+ T cells. The proportion of regulatory T cells was inversely correlated to B-cell proliferation, indicating suppressive ability of these cells. All strains were equally able to colonize the germ-free gut, initially achieving 1010CFU/g faeces, which decreased to 105 over a period of six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improved capacity to develop tolerance compared to germ-free mice. These results suggest that colonization by S. aureus producing superantigens may improve active tolerance to gut allergens.

Distinct roles of the anaphylatoxins C3a and C5a in dendritic cell-mediated allergic asthma.

Conventional dendritic cells (cDC) are necessary and sufficient to drive mixed maladaptive Th2/Th17 immune responses toward aeroallergens in experimental allergy models. Previous studies suggest that the anaphylatoxin C3a promotes, whereas C5a protects from the development of maladaptive immunity during allergen sensitization. However, only limited evidence exists that such effects are directly mediated through anaphylatoxin-receptor signaling in cDCs. In this study, we assessed the impact of C3a and C5a on cDC-mediated induction pulmonary allergy by adoptively transferring house dust mite (HDM)-pulsed bone marrow-derived DCs (BMDC) from wild-type (WT) C3aR(-/-), C5aR1(-/-), or C3aR(-/-)/C5aR1(-/-) into WT mice. Transfer of HDM-pulsed WT BMDCs promoted a strong asthmatic phenotype characterized by marked airway resistance, strong Th2 cytokine, and mucus production, as well as mixed eosinophilic and neurophilic airway inflammation. Surprisingly, C3aR(-/-) cDCs induced a strong allergic phenotype, but no IL-17A production, whereas HDM-pulsed C5aR1(-/-) cDCs failed to drive pulmonary allergy. Transfer of C3aR(-/-)/C5aR1(-/-) cDCs resulted in a slightly reduced allergic phenotype associated with increased IFN-γ production. Mechanistically, C3aR and C5aR1 signaling is required for IL-23 production from HDM-pulsed BMDCs in vitro. Furthermore, C3aR(-/-) BMDCs produced less IL-1β. The mechanisms underlying the failure of C5aR1(-/-) BMDCs to induce experimental allergy include a reduced capability to migrate into the lung tissue and a decreased potency to direct pulmonary homing of effector T cells. Thus, we uncovered a crucial role for C5a, but only a minor role for C3a in BMDC-mediated pulmonary allergy, suggesting that BMDCs inappropriately reflect the impact of complement on lung cDC-mediated allergic asthma development.

Immune modulation promoted by probiotic fermented milk in the mucosal immune system in an experimental model of allergy

Fil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Tucuman. Centro de Referencia para Lactobacilos; Argentina

Developmental Phases of Inflammation-Induced Massive Lymphoid Hyperplasia and Extensive Changes in Epithelium in an Experimental Model of Allergy

Direct evidence that inflammation is linked to carcinogenesis has yet to be established. Very few data are available on the developmental phases of inflammation-induced immune dysfunction that may lead to tumorigenesis. In a series of studies conducted in the 1980s and 1990s, an experimental model of acute and chronic inflammation was established in guinea pig conjunctiva by topical application of fluoresceinyl ovalbumin (FLOA) for up to 30 months. In this updated report, some of the findings are reanalyzed and expanded to identify that at lease 3 developmental phases were involved during the entire course of inflammatory responses including (1) an acute response (phase A) involving IgE-mast cell sensitization and degranulation; (2) an intermediate phase (phase B), a desensitization phenomenon and loss of mast cell function and neovascularization; (3) a chronic response (phase C) and induction of massive lymphoid hyperplasia, follicular formation with germinal centers, increased swollen goblet cells, extensive epithelial thickening and thinning, and angiogenesis. The results suggest evidence of a direct association between inflammation and the development of tumor-like lesions in lymphoid tissues and extensive changes in adjacent epithelia. Confirmation that inflammation induces irreversible changes in lymphoid and epithelial tissues leading to lymphoid tumorigenesis and/or carcinogenesis requires further studies. Understanding the developmental phases of immune dysfunction may provide unique opportunities for diagnosis and treatment of inflammatory diseases, autoimmune disorders, and cancers including lymphomas associated with Sjogren syndrome, squamous cell carcinoma of the conjunctiva, and other lymphomas or epithelial cancers. It is suggested that inflammatory mediators are ideal targets (biomarkers) for diagnosis, chemoprevention, and therapy for several cancers.

Cyclooxygenase Inhibitor Ketorolac or Mast Cell Stabilizers: Immunologic Challenges in Cancer Therapy

Cyclooxygenase Inhibitor Ketorolac or Mast Cell Stabilizers: Immunologic Challenges in Cancer Therapy

The Effect of Lactobacillus casei on an Experimental Model of Atopy

The immunomodulation of IgE synthesis in the allergic process mediated by the Th1/Th2 cytokine balance is now better understood. Lactic acid bacteria (LAB) are used as microorganisms to improve health. Also well demonstrated is the effect of these bacteria as an adjuvant on the mucosal and systemic immune response. These previous reports lead us to study if some LAB, such as Lactobacillus casei strain CRL 431 which has been determined its immunopotentiator capacity, is able to modulate IgE synthesis in a mouse experimental model of allergy induced with ovalbumin. Animals were sensitized with ovalbumin by injection and aerolization. A challenge with the antigen after four weeks of IgE induction was done. L.casei was administered for 2 days at a concentration of 10 9 cells day -1 before sensitization, before challenge, before sensitization, and before and after challenge. In the control animal, an increase in the IgE levels, with diminution in the IFN- n production and high level of IL-4 release was observed. In the animal treated with L.casei a down regulation of IgE synthesis by increasing of IFN- n and diminution of IL-4 cytokines was determined. This effect was only observed when L. casei was administered before sensitization, but not before challenge. These results would indicate that the L. casei would induce Th1 activation able to increase IFN- n cytokine with diminution of IL-4 released by Th2 lymphocytes avoiding the switch toward IgE synthesis. However, L. casei does not have an effect when Th2 are triggered and IL-4 levels are increased. The strain L. casei CRL 431 would be able to modulate Th1/Th2 cytokine balance.