Malnutrition alters the rates of apoptosis in splenocytes and thymocyte subpopulations of rats

Abstract

SummaryMalnutrition continues to be a major public health problem throughout the developing world. Nutritional deficiencies may be the most common cause of secondary immunodeficiency states in humans. It has been suggested that nutritional imbalances can induce apoptosis in a variety of cell types. The purpose of this study was to examine the effect of severe malnutrition on cell subsets and the frequency of spontaneous and/or dexamethasone-induced cell death in vivo in the thymus and spleen from severely malnourished, lactating rats. Apoptosis frequency was estimated by flow cytometry using annexin-V and terminal transferase-mediated dUTP nick-end labelling assay assays. The results obtained in the present study indicate that malnutrition is associated with a significant increase of spontaneously apoptotic cells in the thymus (9·8-fold) and spleen (2·4-fold). Increase in apoptosis was associated largely with CD4 + CD8 + double-positive thymocytes. Unexpectedly, similar frequencies of spontaneous apoptosis of these cells were found in both wellnourished and malnourished rats. In contrast, consistent increases in the apoptosis of CD4 -CD8 -double-negative thymocytes were observed in malnourished rats. In addition, single-positive CD8+ and single-positive CD4 + thymocytes had higher frequencies of apoptosis in malnourished rats. The frequency of total dexamethasone-induced apoptosis was found to be similar in both groups of animals. Nevertheless, in malnourished dexamethasonetreated animals, the percentage of apoptotic double-negative thymocytes was significantly higher than in well-nourished animals, while the rate of apoptosis was lower among double-positive cells. In general, the thymus appears more sensitive to the effects of malnutrition and dexamethasone than the spleen. Furthermore, double-negative thymocytes appear to be the most affected.Keywords: apoptosis, cell death, lymphoid atrophy, malnourished, spleen, thymus

Moderate physical training attenuates perinatal low-protein-induced spleen lymphocyte apoptosis in endotoxemic adult offspring rats

“…These observations are in accordance to previous studies that verified alterations in the dynamic of peripheral leukocytes in response to the acute phase of sepsis in perinatal LP rats [13,42,43]. It is possible that perinatal low-protein profoundly alter cell-counting immune responses as thymic atrophy and the production of thymic hormones critical for the differentiation of T lymphocytes [9,15,40]. In addition, our recent study using the same experimental design attributed the perinatal low-protein diet-induced changes to the high concentrations of plasma corticosterone [13].…”

“…Maternal nutritional deficits can induce apoptosis in various cell types including thymus and spleen and also can affect the embryogenesis of lymphoid organs and result in an impaired expansion of leukocytes causing a deficit of the splenic microanatomy [5,9]. In the present study, there was an expected increase in the relative spleen weight and a high rate of apoptosis in endotoxemic LP rats.…”

“…Neonatal undernutrition (multideficient diet with 7 % of protein) induced a decreased nitric oxide release by alveolar macrophage in vitro of adult rats when compared to their control whose mothers fed a normal diet (23 % of protein) [8]. Previous studies have shown that dietary deficiencies of specific nutrients, for example protein, severely alter the immune responses with significant changes in the immunocompetence as reduced number of T lymphocytes with a memory phenotype and deficits in cell-mediated immunity, involution of lymphoid tissues (thymus and spleen), and suppression of antibody responses to vaccination [5,7,[9][10][11].…”

“…During the immune response, TCD8+ lymphocytes act in association with macrophages to stimulate phagocytosis of blood-borne bacteria that is an important mechanism for protection against viral infection and parasites such as plasmodium [12]. Because splenic development mainly occurs in utero and in the early postnatal life, a nutritional insult at a critical stage on the development of the spleen may lead to a permanent impairment in T lymphocyte immunity, splenic involution and atrophy, circulation of immature lymphocytes, and high splenic lymphocytes apoptosis [5,9,12,14,15]. Malnourished rats (litters with 16 pups) showed a reduction in absolute and relative numbers of splenic lymphocyte subpopulations [14].…”

Influência da L-glutamina sobre aspectos imunomodulatórios de células tronco mesenquimais medulares em situação de desnutrição proteico-energética

“…A DPE está frequentemente associada à imunodeficiência, pois altera diversos aspectos das imunidades inata e adaptativa (CHANDRA, 1997;MARCOS, 2000), desde a ontogenia de suas células até a capacidade efetora das mesmas quando já diferenciadas e maduras (CHANDRA, 2003;ORTIZ et al, 2009;FOCK, ROGERO, et al, 2010;HICKMAN et al, 2014).…”