Avaliação dos efeitos protetores de Lactobacillus delbrueckii UFV-H2b20 em modelo experimental de aspergilose pulmonar

Abstract

The term probiotic is defined as “viable microorganisms, which when administered in adequate amounts, confer benefits to the host”. The use of probiotics has become increasingly studied and recent evidence has suggested that probiotics can provide therapeutic benefits not only directly in the intestine, but also in diseases located in other organs, including the lung. The microorganism L. delbrueckii UFV-H2b20 can be considered a probiotic because it fulfills the basic requirements that a microbial strain needs to be classified as such. Some studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the host's immune system, but its influences on the response to respiratory diseases are still being studied. A. fumigatus is a ubiquitous and saprophytic fungus, responsible for causing about 90% of infections caused by Aspergillus genus, ranging from superficial skin infections to invasive internal organs infections. This type of infection occurs after inhalation of air-dispersed conidia, which are deposited in alveolar spaces, which culminates in the activation of macrophages and the initiation of an inflammatory response. Therefore, the objective of this study was to evaluate the protective effects of the administration of L. delbrueckii UFV-H2b20 in a model of experimental pulmonary infection caused by A. fumigatus in mice. Our results indicate a previous modulation of the immune system caused by L. delbrueckii UFV H2b20, before A. fumigatus infection, with increasing numbers of macrophages, tolerogenic dendritic cells and regulatory T cells FoxP3+ numbers in mesenteric lymph nodes and increasing IgA levels in treated animal’s feces. After infection, we observed increased survival and decreasing fungal burden in the treated group. Furthermore, a decreasing vascular permeability at the site of infection and changes on the recruited cell profile were observed. Results also indicate optimization of neutrophil function such as killing and ROS production, in addition to an increasing macrophage epherocytosis. Finally, treated animals also had higher Treg amounts and higher TGF-β and IL-10 concentrations, with a consequent decreased production of IL1-β, IL-17 and CXCL-1, indicating greater inflammatory regulation. We also observed evidence of protection caused by the lactate metabolite, the main metabolite produced by L. delbrueckii UFV H2b20. This protection is represented by increased survival lactate treated mice infected with A. fumigatus compared to not treated infected mice, thus indicating a possible probiotic mechanism of action. Thus, our results indicate the potencialization of immune responses that are important for controlling A. fumigatus infection, promoted by L. delbrueckii UFV H2b20 ingestion, which involves innate immune response optimization and regulation during early infection, leading to lower susceptibility of hosts to infection.