Avaliação da influência da dieta materna em modelo experimental murino de asma alérgica

Abstract

Maternal obesity and the consumption of high-fat diets increase the risk of several complications in the offspring, including the development of asthma at any age, through mechanisms that are not fully understood. The concomitance of both diseases promotes distinct phenotypes, which can be characterized by an aggravated Th2 phenotype and eosinophilia, or even a mixture of Th1 and Th2 responses in childhood. While in adulthood, there is an increase in the Th17 profile response and neutrophilic inflammation. Regardless of the profile, in most cases, symptoms are exacerbated and resistant to corticosteroid treatment. Obesity and maternal obesogenic diets can also influence the colonization of the progeny, favoring the formation of a harmful intestinal microbiota. However, there are still no studies that evaluate the impact of maternal diet on the composition of the lung microbiota of the offspring. The aim of this study was to explore the immunological modifications by which maternal diet may affect asthma risk and/or worsen asthma symptoms, as well as modify lung colonization. For this, matrices of BALB/c mice fed with diet (HFD) or standard (SD) for 8 weeks were mated and their offspring were used in the experiment. Asthma was induced by sensitization to Ovalbumin on the 7th and 14th days of life, followed by three intranasal challenges on the 21st-23rd days, the mice were euthanized on the 24th day. The animals were weighed, lung, colon, spleen, lymph nodes and bone marrow were collected for histological analysis and immunophenotyping. A preliminary analysis of the lung microbiota was performed by Rep-PCR. Blood was collected for metabolic analysis and dosage of antigen-specific antibody levels. The results showed that the HFD dams did not show significant weight gain, but there was an increase in leptin and LDL cholesterol levels. When evaluating the effects of maternal diet on offspring regardless of asthma status, offspring of HFD females had higher body mass, higher glucose levels, lower HDL cholesterol levels and higher expression of CD86 and PDL1 in lung and splenic cells. There was an increased expression of GATA3 in the spleen and lung. On the other hand, RORγT showed an increased expression in the spleen, but reduced in the mediastinal lymph nodes and in the lung, when compared to offspring from SD dams. The maternal high-fat diet also decreased CD80 expression on LPSstimulated bone marrow-derived dendritic cells and increased PDL1 expression on the same unstimulated cells. After asthma induction, asthmatic pups from HFD dams had higher eosinophil and mast cell counts in lung tissue, higher IgG2a titers, and lower IgG1 and IgE titers compared to asthmatic pups from SD dams. In addition, asthma had a more significant impact on lung bacterial composition when compared to maternal diet. Taken together, the results demonstrate that consumption of a high-fat diet before and during pregnancy can affect the immune response of the offspring, an effect mediated in part by inappropriate activation of dendritic cells, which occurred even before the induction of asthma. This event may contribute to an increase in eosinophilic inflammation, but a reduction in atopy.