Insulin‐like Growth Factor (IGF)‐I affects parasite growth and host cell migration in experimental cutaneous leishmaniasis

Abstract

While the control or progression of leishmaniasis depends on host immune responses, the initial inflammatory process represents a key event. This process involves the participation of several cytokines and growth factors induced during inflammation as well as factors already present at the site of infection such as insulin-like growth factor (IGF)-I. We have previously demonstrated a potential role for IGF-I in experimental cutaneous leishmaniasis based on the significant increase in lesion size seen in mice injected with Leishmania promastigotes preactivated with IGF-I. In the present study we show that preactivation of Leishmania (Leishmania) amazonensis promastigotes with IGF-I induces an increase in the actual number of parasites at the lesion site from seven days postinfection, in addition to a more intense inflammatory infiltrate. There was a higher numerical density of polymorphonuclear neutrophils from 3 to 24 h, and of mononuclear cells from 48 h of infection onward. A higher density of polymorphonuclear neutrophils and mononuclear cells harboring parasites was also observed. The most important observation, however, was that more parasites per cell were present, revealing that IGF-I appears to favour parasite growth within the macrophages. These results strongly suggest an important role for IGF-I in the development of cutaneous leishmaniasis, where it influences both the inflammatory process and parasite growth.

Macrophage Interactions with Neutrophils RegulateLeishmania majorInfection

“…Killed BALB neutrophils exacerbated parasite loads in draining lymph nodes in vivo. An early influx of neutrophils to infected tissue has been associated with susceptibility to infection by L. major (17) and L. amazonensis (37). Our results agree with these studies.…”

Insulin-Like Growth Factor-I Induces Arginase Activity inLeishmania amazonensisAmastigote-Infected Macrophages through a Cytokine-Independent Mechanism

“…In experimental models, extrinsic IGF-I significantly increases lesion sizes and the number of viable parasites [21]. …”

Dihydrotestosterone enhances growth and infectivity of Leishmania Mexicana

“…L. mexicana amastigotes were isolated from footpad lesions of BALB/c mice infected 6‐8 weeks earlier, as previously described . Promastigotes were obtained by culturing isolated amastigotes at 26°C in culture medium 199, pH 7.2, supplemented with 10% heat‐inactivated foetal bovine serum (FBS), 100 U/mL penicillin G, 100 μg/mL streptomycin and 2 mM L‐glutamine (all from Gibco‐Life Technologies, Grand Island, NY, USA) and subpassaged during the logarithmic growth phase (days 3‐4 of culture).…”

“…mexicana amastigotes were isolated from footpad lesions of BALB/c mice infected 6-8 weeks earlier, as previously described. [28][29][30][31] Promastigotes were obtained by culturing isolated amastigotes at 26°C in culture medium 199, pH 7.2, supplemented with 10% heat-inactivated foetal bovine serum (FBS), 100 U/mL penicillin G, 100 μg/mL streptomycin and 2 mM L-glutamine (all from Gibco-Life Technologies, Grand Island, NY, USA) and subpassaged during the logarithmic growth phase (days 3-4 of culture). For in vitro and in vivo infections, promastigotes from the stationary growth phase (day 5 of culture) were used, which corresponds to the day when most promastigotes have transformed into highly infective metacyclic promastigotes.…”