O papel das proteínas da dieta na maturação do sistema imune após o desmame e na infecção experimental por Leishmania major

Abstract

The majority of contacts with foreign antigenic materials occurs on the gut mucosa, and is represented by food proteins and the microbiota. Approximately 30 kg of food proteins reach the human intestine per year and 130±190 g of these proteins are absorbed daily in the gut (Mestecky, 1987). Recently, we described a mouse model where we replaced intact dietary proteins with equivalent amounts of amino acids (Aa) from weaning and investigated its effects on the development of the immune system. We observed that adult animals reared on a balanced protein-free diet (Aa-mice) have a poorly developed gut-associated lymphoid tissue resembling suckling mice. In vitro cytokine production by cells from several lymphoid organs shows a predominant Th2 profile with a high concentration of IL-10 and IL-4, and a low concentration of IFN-g (Menezes e cols., 2003). In this study, we observed that introduction of a protein-containing diet to mice treated with Aa diet from weaning up to 8 weeks of age recover ed their immunoglobulin levels in three days. This recovery is dependent on the amount of protein present in the diet. At least 10% of casein are necessary to promote normal standards of GALT development and immunoglobulin production. To study the role of dietary proteins in development of infectious disease, we infected mice that were treated with Aa diet with Leishmania major. Mice that were fed Aa diet since weaning were inoculated with 1 million parasites and lesion development was followed for 4 weeks. Aa mice show an increase in footpad lesion and parasite load as well as a reduction in IFN-g production by in vitro stimulated popliteal lymph node cells when compared to control mice. In addition, Aa diet-fed mice have a decreased expression of CD40 in macrophages and CD80 in dendritic cells when compared to control mice. Interestingly, antigen presenting cells from Aa-mice and from 3 week-old pre-weaning mice have a similar level of expression of co-stimulatory molecules such as CD40, CD80 and CD86.Our data indicates that stimulation by dietary proteins has a physiological role in maturation of immune system probably by activating antigen presenting cells and, as a consequence, T lymphocytes. The immature state of Aa-fed C57BL/6 mice seems to interfere in their ability to clear infection with Leishmania major.