MALNUTRITION IMPACTS PROTECTIVE IMMUNE RESPONSES AND MUCOSAL IMMUNITY DURING VISCERAL LEISHMANIASIS

Abstract Protein malnutrition is a risk factor for developing visceral leishmaniasis (VL) due to defective immune responses that culminate in early visceralization. The intestine is a target of both malnutrition and infection, but the immunological events that occur there during infection are unknown. We postulated that malnutrition exacerbates VL due to defective immunological mechanisms to control parasite replication in the spleen and liver, and by modifying intestinal mucosal immunity. To study the effect of malnutrition on immune response in chronic VL we used a polynutrient deficiency (deficient protein, energy, zinc, and iron) diet which mimics moderate human malnutrition followed by Leishmania infantum infection. The polynutrient deficient diet leads to growth stunting, reduced mass, and cellularity of the spleen, liver, and mesenteric lymph node (MLN). Malnourished-infected mice were more susceptible to infection, harboring more parasites in the spleen and liver. Flow cytometry analysis revealed a reduced number of T lymphocytes, and reduced production of IFN-γ by T cells in malnourished-infected mice. In the MLN, L. infantum infection induced the production of IFN-γ and TNF, while malnourished-infected mice exhibited a significant decrease in the IFN-γ production by T cells. Also, malnourished-infected mice presented a reduction in the IL-17 and IL-22 production by CD4+ cells, which are critical components for intestinal integrity and homeostasis. Together, malnutrition causes a defective IFN-γ-mediated response and promotes dysfunctional mucosal immunity which increases susceptibility in VL.