Abstract
Leishmaniases are diseases caused by several Leishmania species, and many factors contribute to the development of the infection. Because the adaptive immune response does not fully explain the outcome of Leishmania infection and considering that the initial events are crucial in the establishment of the infection, we investigated one of the growth factors, the insulin-like growth factor-I (IGF-I), found in circulation and produced by different cells including macrophages and present in the skin where the parasite is inoculated. Here, we review the role of IGF-I in leishmaniasis experimental models and human patients. IGF-I induces the growth of different Leishmania species in vitro and alters the disease outcome increasing the parasite load and lesion size, especially in L. major- and L. amazonensis-infected mouse leishmaniasis. IGF-I affects the parasite interacting with the IGF-I receptor present on Leishmania. During Leishmania-macrophage interaction, IGF-I acts on the arginine metabolic pathway, resulting in polyamine production both in macrophages and Leishmania. IGF-I and cytokines interact with reciprocal influences on their expression. IL-4 is a hallmark of susceptibility to L. major in murine leishmaniasis, but we observed that IGF-I operates astoundingly as an effector element of the IL-4. Approaching human leishmaniasis, patients with mucosal, disseminated, and visceral diseases presented surprisingly low IGF-I serum levels, suggesting diverse effects than parasite growth. We observed that low IGF-I levels might contribute to the inflammatory response persistence and delayed lesion healing in human cutaneous leishmaniasis and the anemia development in visceral leishmaniasis. We must highlight the complexity of infection revealed depending on the Leishmania species and the parasite's developmental stages. Because IGF-I exerts pleiotropic effects on the biology of interaction and disease pathogenesis, IGF-I turns up as an attractive tool to explore biological and pathogenic processes underlying infection development. IGF-I pleiotropic effects open further the possibility of approaching IGF-I as a therapeutical target.
Highlights
Leishmaniases are considered neglected tropical diseases caused by parasites of the order Kinetoplastida, family Trypanosomatidae, and genus Leishmania, affecting one million people globally each year and endemic in 98 countries
We initially present some data related to the involvement of adaptive immune response on Leishmania major and Leishmania donovani/Leishmania infantum infections that do not fully clarify infection development to justify the focus here on nonspecific factors
Moving to in vivo studies using a cutaneous leishmaniasis model in BALB/c mice, we have shown that the preincubation of L. amazonensis promastigotes with insulin-like growth factor-I (IGF-I) promotes a significant increase in the footpad lesion size, 21 days postinfection
Summary
Leishmaniases are considered neglected tropical diseases caused by parasites of the order Kinetoplastida, family Trypanosomatidae, and genus Leishmania, affecting one million people globally each year and endemic in 98 countries. The infection can be asymptomatic or symptomatic, leading to a wide spectrum of clinical manifestations ranging from localized, disseminated, or diffuse cutaneous lesions or Journal of Immunology Research mucosal lesions to viscera involvement such as the liver and spleen [1]. The establishment of these different clinical forms depends on the parasite’s species and on the vector, in addition to the epidemiological characteristics and genetic and immunological constitution of the host [2], where both innate and adaptive immune responses can drive the development or control of infection. We present data including studies on the innate immune response that points out our research on the IGF-I growth factor as an element that may contribute to Leishmania infection
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