Leishmania (Viannia) braziliensisamastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection

Abstract

Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate.

Fcγ‐RI, Fcγ‐RII and IL‐10 as predictive biomarkers for post‐therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients

“…Moreover, we demonstrated that Glucantime ® treatment changes the monocyte functional profile to a more effective proinflammatory. Although Glucantime ® is known for immunomodulatory mechanisms, it increases the in vitro and ex vivo production of NO and in vitro TNF‐α suggesting that it has an anti‐ L. braziliensis action that is important for parasite clearance . These findings showed that treatment with Glucantime ® creates a microenvironment unfavourable to parasite growth.…”

Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species

“…braziliensis in human macrophages. Therefore, we evaluated microbicidal molecules known to be involved in Leishmania control [30,54,55] as possible targets of IL-32γ. Our data demonstrate that IL-32γ is linked with the induction of iNOS, cathelicidin and β-defensin 2 expression and consequently NO, LL-37 peptide, and β-defensin 2 release during Leishmania species infection.…”

“…These molecules were induced by IL-32 in influenza virus [48] and MTB infection [8]. NO is a classical leishmanicidal molecule in mouse macrophages [30] but human macrophages produce low levels of NO. Nevertheless, in some reports this was enough to contribute for Leishmania killing [56–58].…”

The Presence of Leishmania braziliensis DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study

“…Another possibility is that the parasite disseminates later in the disease process. It has been suggested that amastigotes from ML patients have a decreased ability to be internalized and grow more slowly than those from CL patients ( Gomes et al., 2016 ) and that stationary phase promastigotes from ML are more resistant to nitric oxide ( Ávila et al., 2018 ). These findings suggest that ML parasites are transmitted by vectors as promastigotes that are initially more resistant and more likely to disseminate ( Ávila et al., 2018 ).…”

“…In another study by Gomes et al, IFN-γ knockout (KO) mice were infected with amastigotes from patients with ML and CL. Interestingly, in mice infected with ML-derived amastigotes, cutaneous lesions appeared later, but a greater number of parasites were observed in the spleen ( Gomes et al., 2016 ). The same group later showed that the stationary-phase promastigotes derived from ML are more resistant to killing by nitric oxide (NO) and reactive oxygen species than are the CL-derived promastigotes.…”