Promastigote parasites cultured from the lesions of patients with mucosal leishmaniasis are more resistant to oxidative stress than promastigotes from a cutaneous lesion

Abstract

Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species (ROS). The aim of this study was to evaluate the ability of parasites obtained from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and amastigotes from LCL or ML isolates produced similar amounts of NO in culture. Promastigotes from ML isolates were more resistant to NO and HO than LCL parasites in a stationary phase, whereas amastigotes from LCL isolates were more resistant to NO. In addition, in the stationary phase, promastigote isolates from patients with ML expressed more thiol-specific antioxidant protein (TSA) than LCL isolates. Therefore it is suggested that infective promastigotes from ML isolates are more resistant to microbicidal mechanisms in the initial phase of infection. Subsequently, amastigotes lose this resistance. This behavior of ML parasites can decrease the number of parasites capable of stimulating the host immune response shortly after the infection establishment.

The Influence of Infection by Different Leishmania (Viannia) braziliensis Isolates on the Pathogenesis of Disseminated Leishmaniasis

“…Ávila et al showed that L. (V.) braziliensis promastigotes and amastigotes isolated from CL and ML patients produced similar amounts of NO in culture. However, promastigotes from ML isolates were found to be more resistant to NO and H 2 O 2 than CL parasites (Avila et al, 2018). Our results document that infection with DL isolates induces higher respiratory burst in monocytes from DL, CL and HS compared to isolates from CL, yet the observed enhancement in oxidative burst did not inhibit parasite multiplication, which suggests that DL isolates are less susceptible to monocyte killing than CL.…”

Genotypic Differences among Isolates of L. Braziliensis and Host Factors in The Pathogenesis of Disseminated Leishmaniasis

“…Ávila et al showed that L. braziliensis promastigotes and amastigotes isolated from CL and ML patients produced similar amounts of NO in culture. However, promastigotes from ML isolates were found to be more resistant to NO and H 2 O 2 than CL parasites 42 . Our results document that infection with DL isolates induces higher respiratory burst in monocytes from both DL and CL patients compared to isolates from CL, yet the observed enhancement in oxidative burst did not inhibit parasite multiplication, which suggests that DL isolates are less susceptible to monocyte killing than CL.…”

Leishmania Spp-Host Interaction: There Is Always an Onset, but Is There an End?

“…In contrast, L. naiffi , which generally causes a benign and autoresolutive infection in humans, showed the lowest infection index and the highest NO production (Campos et al, 2008). In another study, promastigotes isolated from patients with mucosal leishmaniasis express more thiol-specific antioxidant protein, and were more resistant to nitric oxide and H 2 O 2 than strains obtained from localized cutaneous leishmaniasis (Ávila et al, 2018). Leishmania amazonensis , which is capable of inducing severe diffuse cutaneous form cursing with high parasite load and inactivation of macrophages, also developed strategies to escape from oxidative effects from phagocytes.…”

“…Two natural events proving the persistence of parasite are represented by 1- mucosal lesions produced years after primary cutaneous lesions (Leite et al, 2012; Ávila et al, 2018), and 2- the Post-Kal-azar dermal leishmaniasis (PKDL) after VL recovering (Ganguly et al, 2010; Singh et al, 2012; Zijlstra, 2016). In both cases, the same Leishmania species is able to produce, after healing, a different clinical form from primary manifestations.…”