Leishmania braziliensis isolated from disseminated leishmaniasis patients downmodulate neutrophil function.

Thiago Cardoso,Caroline Bezerra,Rajendranath Ramasawmy,Lilian Silva Medina,Olívia Bacellar,Albert Scheriefer,Edgar M De Carvalho

doi:10.1111/pim.12620

Abstract

SummaryAimsThe polymorphism observed in Leishmania braziliensis is associated with different clinical forms of leishmaniasis. Neutrophils (PMNs) participate in the pathogenesis of leishmania infection, and here, we evaluate neutrophil function after infection with isolates of L. braziliensis from cutaneous leishmaniasis (CL) or disseminated leishmaniasis (DL) patients.Methods and resultsNeutrophils from 30 healthy subjects (HS) were infected with isolates of L. (V.) braziliensis obtained from three CL and three DL patients. They were infected at the ratio of 3:1 parasites per neutrophil, and leishmania uptake was evaluated by microscopy. The neutrophil activation markers and oxidative burst by expression of dihidrorhodamine (DHR) were evaluated by flow cytometry and cytokine production by ELISA. The frequency of infected cells and the number of amastigotes were higher in neutrophils infected with CL isolates compared to DL isolates (P < 0.05). The DHR and CD66b expression after infection with DL isolate was lower than with CL isolates. There was no difference regarding chemokine production.ConclusionThe L. (V.) braziliensis isolates of DL induced lower respiratory burst and neutrophils activation markers compared with CL isolates which may contribute to parasite survival and dissemination in DL patients.

Highlights

The American tegumentary leishmaniasis (ATL) is caused pre‐ dominantly by L. (V.) braziliensis, a parasite that is associated with different clinical forms of the disease as cutaneous, mucosal and disseminated cutaneous leishmaniasis (DL).[1,2] The cutaneous leishmaniasis (CL) is the most common presentation of the dis‐ ease occurring in over 90% of the cases and is characterized by a well‐limited skin ulcer with raised borders
Initial studies showed that DL patients have more negative leishmania skin de‐ layed type hypersensitivity test (LST) and an impairment in lym‐ phocyte proliferation and in the production of interferon‐γ and TNF in supernatants of mononuclear cells stimulated with soluble leishmania antigen (SLA) as compared to CL patients.[8]
We have previously shown that neutrophils from CL produce higher levels of reactive oxygen species and pro‐inflammatory cytokines than healthy subjects neutrophils upon L. (V.) braziliensis infection.[16]

Summary

Introduction

The American tegumentary leishmaniasis (ATL) is caused pre‐ dominantly by L. (V.) braziliensis, a parasite that is associated with different clinical forms of the disease as cutaneous, mucosal and disseminated cutaneous leishmaniasis (DL).[1,2] The cutaneous leishmaniasis (CL) is the most common presentation of the dis‐ ease occurring in over 90% of the cases and is characterized by a well‐limited skin ulcer with raised borders. (V.) braziliensis, a parasite that is associated with different clinical forms of the disease as cutaneous, mucosal and disseminated cutaneous leishmaniasis (DL).[1,2] The cutaneous leishmaniasis (CL) is the most common presentation of the dis‐ ease occurring in over 90% of the cases and is characterized by a well‐limited skin ulcer with raised borders. 3% of CL patients develop concomitantly or months and sometimes years after the cutaneous disease, mucosal leishmaniasis (ML) that affect primarily the nasal mucosa.[3] DL is an emerging clinical form of ATL defined by the presence of ten up to more than 1000 ac‐ neiform, papular and ulcerated lesions in at least two parts of the body.[4] In the majority of the cases, DL patients present initially as a typical CL ulcer, and after 1 or 2 weeks or sometimes even. These data suggest that parasite, more than host factors, may be involved in the pathogenesis of DL

Results

Discussion

Conclusion