Malnutrition disrupts adaptive immunity during visceral leishmaniasis by enhancing IL-10 production

Abstract

Protein-energy malnutrition (PEM) is a risk factor for developing visceral leishmaniasis (VL). However, the impact on adaptive immunity during infection is unknown. To study the effect of malnutrition on chronic VL, we used a polynutrient-deficient diet (deficient protein, energy, zinc, and iron), which mimics moderate human malnutrition, followed by Leishmania infantum infection. The polynutrient-deficient diet leads to growth stunting and reduced mass of visceral organs. Malnourished-infected mice harbored more parasites in the spleen and liver, had a reduced number of T lymphocytes, reduced production of IFN-{gamma} by T cells, and exhibited enhanced IL-10 production. To test whether IL-10 blockade would lessen disease in the malnourished mice, we treated infected mice with monoclonal antibody -IL-10R. -IL-10R treatment reduced the parasite number of malnourished mice, restored the number of T cells producing IFN-{gamma}, and enhanced hepatic granuloma formation. Our results indicate that malnutrition increases VL susceptibility due to a defective IFN-{gamma}-mediated immunity attributable to increased IL-10 production. Author SummaryMalnutrition contributes to the development of VL. Despite the advances regarding this association, how malnutrition affects the adaptive immune mechanisms in VL is still unclear. We found that malnutrition disrupts the ability to control parasite replication in the spleen and liver in VL due to defective IFN-{gamma}-mediated immunity, reduced hepatic granuloma formation, and enhanced IL-10 production. Blocking IL-10R signaling restored the protective mechanisms to control parasite replication in the malnourished mice without interfering with the undernutrition state. Thus, we demonstrate that malnutrition disrupts the adaptive immunity against VL due to an aberrant IL-10 production. Understanding the association between malnutrition and VL will provide insights into therapeutic approaches.