Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum

Abstract

Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals.

Assessment of nutritional stress in famine burials using stable isotope analysis

“…The authors argue that the individuals who exhibited signs of generalized infection at death likely consumed a diet lower in terrestrial animal protein, increasing their susceptibility to pathogens that led more frequently to generalized infections. This is consistent with the findings from numerous studies in humans and animal models that protein malnutrition influences the immune system (Calder, 2013; Li, Yin, li, Kim, & Wu, 2007; Losada‐Barragán et al, 2017). Thus, the lower proportion of protein consumed by individuals facing famine in this study could have increased their susceptibility to infection and eventually death.…”

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring

“…These cells will undergo final maturation in peripheral lymphoid organs (26) . While early malnutrition in postnatal life impairs thymic development and immune function at young ages (11,12,(27)(28)(29) , few animal studies report the consequences of intra-uterine growth restriction (IUGR) induced by fetal malnutrition on thymic structure and function at adulthood. The purpose of the present study is to describe the consequences of maternal malnutrition during gestation on thymic growth, thymic structure and the proportions of thymocyte and lymphocyte subpopulations in adult rat offspring.…”

Congenital Zika syndrome is associated with maternal protein malnutrition

“…It has been reported that CZS is more prevalent in low-income populations (9,11). Nutritional impairment has been found to result in the compromise of several innate and adaptive pathways of the immune system (25)(26)(27)(28). Mainly, protein restriction is an issue in those vulnerable populations with limited access to more expensive food components (14).…”