Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection

Malnutrition is a risk factor for the development of visceral leishmaniasis . However, the immunological basis for this susceptibility is unknown. We h ave developed a mouse model to study the effect of malnutrition on innate i mmunity and early visceralization following Leishmania donovani infection. Three deficient diets were studied, including 6, 3, or 1% protein; these di ets were also deficient in iron, zinc, and calories. The control diet conta ined 17% protein, was zinc and iron sufficient, and was provided ab libitum . Three days after infection with L. donovani promastigotes, the total extr adermal (lymph nodes, liver, and spleen) and skin parasite burdens were equ ivalent in the malnourished (3% protein) and control mice, but in the malno urished group, a greater percentage (39.8 and 4.0%, respectively; P = 0.009 ) of the extradermal parasite burden was contained in the spleen and liver. The comparable levels of parasites in the footpads in the two diet groups and the higher lymph node parasite burdens in the well-nourished mice indic ated that the higher visceral parasite burdens in the malnourished mice wer e not due to a deficit in local parasite killing but to a failure of lymph node barrier function. Lymph node cells from the malnourished, infected mic e produced increased levels of prostaglandin E-2 (PGE(2)) and decreased lev els of interleukin-10. Inducible nitric oxide synthase activity was signifi cantly lower in the spleen and liver of the malnourished mice. Thus, malnut rition causes a failure of lymph node barrier function after L. donovani in fection, which may be related to excessive production of PGE(2) and decreas ed levels of IL-10 and nitric oxide.