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

• Published in: Scientific reports 2017-04, Vol.7 (1), p.45991-15, Article 45991
• Main Authors: Losada-Barragán, Monica, Umaña-Pérez, Adriana, Cuervo-Escobar, Sergio, Berbert, Luiz Ricardo, Porrozzi, Renato, Morgado, Fernanda N., Mendes-da-Cruz, Daniella Areas, Savino, Wilson, Sánchez-Gómez, Myriam, Cuervo, Patricia
• Format: Article
• Language: English
• Subjects: 13/2; 13/21; 13/51; 38; 38/22; 38/77; 38/90; 631/250/1620/1840; 631/250/255/1715; 64; 64/60; 692/699/1702/295; 82; 82/1; Cell adhesion & migration; Chemotactic factors; CXCL10 protein; CXCL12 protein; Developing countries; Humanities and Social Sciences; Immune response; Immune response (cell-mediated); Immunology; Infections; Insulin-like growth factor I; LDCs; Leishmania infantum; Leukocyte migration; Lymphocytes; Lymphocytes T; Lymphoid tissue; Malnutrition; multidisciplinary; Parasites; Parasitic diseases; Proteins; Risk factors; Rodents; Science; Spleen; Subpopulations; Thymus; Vector-borne diseases; Visceral leishmaniasis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep45991

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.