Impact of genetic polymorphisms related to innate immune response on respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) causes lower respiratory tract infections and bronchiolitis, mainly affecting children under 2 years of age and immunocompromised patients. Currently, there are no available vaccines or efficient pharmacological treatments against RSV. In recent years, tremendous efforts have been directed to understand the pathological mechanisms of the disease and generate a vaccine against RSV. Although RSV is highly infectious, not all the patients who get infected develop bronchiolitis and severe disease. Through various sequencing studies, single nucleotide polymorphisms (SNPs) have been discovered in diverse receptors, cytokines, and transcriptional regulators with crucial role in the activation of the innate immune response, which is implicated in the susceptibility to develop or protect from severe forms of the infection. In this review, we highlighted how variations in the key genes affect the development of innate immune response against RSV. This data would provide crucial information about the mechanisms of viral infection, and in the future, could help in generation of new strategies for vaccine development or generation of the pharmacological treatments.

Lactococcus lactis NZ9000 Prevents Asthmatic Airway Inflammation and Remodelling in Rats through the Improvement of Intestinal Barrier Function and Systemic TGF-ß Production.

INTRODUCTION: The use of probiotics has been broadly popularized due to positive effects in the attenuation of aberrant immune responses such as asthma. Allergic asthma is a chronic respiratory disease characterized by airway inflammation and remodelling. OBJECTIVE: This study was aimed to evaluate the effect of oral administration of Lactococcus lactis NZ9000 on asthmatic airway inflammation and lung tissue remodelling in rats and its relation to the maintenance of an adequate intestinal barrier. METHODS: Wistar rats were ovalbumin (OVA) sensitized and challenged and orally treated with L. lactis. Lung inflammatory infiltrates and cytokines were measured, and remodelling was evaluated. Serum OVA-specific immunoglobulin (Ig) E levels were assessed. We also evaluated changes on intestinal environment and on systemic immune response. RESULTS: L. lactis diminished the infiltration of proinflammatory leucocytes, mainly eosinophils, in the bronchoalveolar compartment, decreased lung IL-4 and IL-5 expression, and reduced the level of serum allergen-specific IgE. Furthermore, L. lactis prevented eosinophil influx, collagen deposition, and goblet cell hyperplasia in lung tissue. In the intestine, L. lactis-treated asthmatic rats increased Peyer's patch and goblet cell quantity and mRNA expression of IgA, MUC-2, and claudin. Additionally, intestinal morphological alterations were normalized by L. lactis administration. Splenocyte proliferative response to OVA was abolished, and serum levels of transforming growth factor (TGF)-ß were increased by L. lactis treatment. CONCLUSIONS: These findings suggest that L. lactis is a potential candidate for asthma prevention, and the effect is mediated by the improvement of intestinal barrier function and systemic TGF-ß production.

Protective Effect of Glycomacropeptide on the Atopic Dermatitis-Like Dysfunctional Skin Barrier in Rats.

The maintenance of a healthy skin barrier is crucial to prevent and treat atopic dermatitis (AD) lesions and avoid infections. Glycomacropeptide (GMP) is a bioactive peptide that has demonstrated promising results as an anti-inflammatory and antipruritic therapy for experimental AD. This study aimed to analyze the effect of GMP on impaired cutaneous barrier-related signs in a rat model of AD lesions. AD-like dermatitis was induced on the skin by repeated topical applications of 2,4-dinitrochlorobenzene, and animals were orally administered GMP before or after AD induction. The expression of skin structural proteins and antimicrobial peptides (AMPs) was evaluated by immunoblot or immunohistochemistry, epidermal thickening was evaluated by histochemistry, the level of IFN-γ and changes in the microbiota were evaluated by quantitative polymerase chain reaction, and the quantity of fecal short-chain fatty acids (SCFAs) was evaluated by gas chromatography. GMP administration significantly increased filaggrin, ß-defensin 2, and cathelicidin-related AMP expression in AD-like lesions. Involucrin expression was not modified. In GMP-treated animals, epidermal thickening and IFN-γ expression were strongly reduced in damaged skin. GMP treatment impacted the skin microbiota and prevented Staphylococcus aureus colonization, which is associated with AD. In addition, high levels of Bifidobacterium were detected in the feces of GMP-treated animals, and the acetic acid and butyric acid contents increased in animals prophylactically administered GMP. These results suggest that GMP markedly prevents or reverses skin barrier damage in rat AD-like lesions through a bifidogenic effect that induces fecal SCFA production with prolonged treatment. Our findings provide evidence that GMP may represent an optimum strategy for the therapy of the dysfunctional cutaneous barrier in AD.