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Local and systemic effects of low-protein unbalanced diets in the gut-mucosa tissue-specific immunity

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Jaqueline Marques Santos
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Denise Morais da Fonseca; Ana Maria Caetano de Faria; Maria Notomi Sato; Angelica Thomaz Vieira
Advisor: Denise Morais da Fonseca

Maintaining homeostasis in mucosal tissues requires the presence of a network of tissue-specific immune mechanisms endowed with the ability to maintain tolerance to environmental antigens and, at the same time, to induce efficient effector responses to prevent invasion by pathogens. In the intestine, in particular, several elements maintain bi-dimensional interactions to maintain the tissue-specific immunity, including the resident microbiota and components of the diet. However, microorganisms (commensals, pathobionts and pathogens) and environmental factors, such as diet (prebiotics, upplements or nutrients), can cause the breakdown of intestinal immunehomeostasis. For instance, changes in diet can modify the composition of commensalmicrobiota, impacting on the local immune response. Thus, this study aimed to evaluate the effects of an unbalanced diet based on carbohydrates and deficient in proteins and lipids (which we will call a low-protein diet) in tissue-specific intestinal immune homeostasis. For this study, C57BL/6 mice were treated with a low-protein diet ad libitum for 6 weeks to assess the cellular infiltrate in the lamina propria. The results obtained show that the treatment with a low-protein diet, although it seems not to result in significant malnutrition or deficit in the animal\'s body development, seems to alter the intestinal mucosal homeostasis. This change was more evident in the proximal portion of the small intestine and was characterized by an increase in the presence of DC subsets associated with canonical intestinal responses (CD103&#43CD11b&#43), as well as an increase in the presence of Treg and Th17 cells in parallel with a type 2 innate cell infiltration (Eosinophils, ILC2 and M2 macrophages). In addition, the diet was associated with a reduction in cell populations of a more inflammatory character, such as neutrophils, monocytes, M1 macrophages, ILC3 and Th1 cells. To assess the functional impact of such changes, mice were infected with a subclinical inoculum of the bacterium Yersinia pseudotuberculosis that did not caused disease in animals fed the control diet, but led to deficit in growth and development of a chronic inflammatory process in the gut mucosa. This effect was not dependent nor on the presence of active infection or the microbiota altered by the infection. In addition to the impaired responses to infectious antigens, treatment with the diet also affected responoses to food-borne antigens. Animals treated with the low protein diet, when exposed to oral Ovalbumin (OVA), exhibited activation of specific T lymphocytes for OVA of the Treg, Th17 and Th2 pattern, unlike the control group where there was na exclusive polarization for a Treg profile. Together, these results show that the use of an unbalanced diet, even if it does not cause an apparent malnutrition, can lead to impaired activation of the tissue-specific immune response of the intestinal mucosa and the development of systemic diseases. (AU)

FAPESP's process: 18/00458-0 - Development of an experimental model of environmental Enteropathy
Grantee:Jaqueline Marques Santos
Support Opportunities: Scholarships in Brazil - Master