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

Walker N Oliveira,Lucas P Carvalho,Maurício T Nascimento,Andreza S Dórea,Pedro P Carneiro,Albert Schriefer,Edgar M Carvalho,Olívia Bacellar,Paulo R L Machado

doi:10.3389/fcimb.2021.740278

Abstract

Disseminated Leishmaniasis (DL) is an emerging and severe form of Leishmania (Viannia) braziliensis infection defined by the presence of 10 and up to more than 1,000 skin lesions. The mechanisms underlying parasite dissemination remain unknown. Genotypic differences among species of L. braziliensis have been associated with different clinical forms of disease. The present work compared the function of monocytes obtained from patients with cutaneous leishmaniasis (CL) and DL in response to infection with L. braziliensis isolates of both these two clinical forms of disease. Mononuclear cells obtained from DL and CL patients were infected with different L. braziliensis isolates, and numbers of infected cells, parasite load, respiratory burst, TLR2 and TLR4 expression and cytokine production were evaluated. DL isolates infected more monocytes, induced greater respiratory burst, and more cytokine production compared to isolates from CL patients regardless of the origin of monocytes (DL or CL). However, greater parasite multiplication and higher TLR2 and TLR4 expression were seen in monocytes from DL patients compared to CL following infection with DL isolates. Our results indicate the participation of both parasite genotype and host factors in the pathogenesis of DL.

Highlights

Disseminated leishmaniasis (DL), a severe form of Leishmania (Viannia) braziliensis infection, is defined by the presence of more than 10, and up to 1,000 papular, acneiform and ulcerated lesions across at least two separate parts of the body (Turetz et al, 2002)
Regardless of donor cell origin, we identified higher frequencies of infected cells and greater numbers of amastigotes per 100 cells in monocytes infected with an isolate from Disseminated Leishmaniasis (DL) compared to cutaneous leishmaniasis (CL) at both 2 and 48 hours after infection (Figures 2A, B)
The median frequency of DL monocytes infected with a CL isolate was 46% (30-58 cells) at 2 hours versus 58% (45-76 cells) for a DL isolate (p

Summary

Introduction

Disseminated leishmaniasis (DL), a severe form of Leishmania (Viannia) braziliensis infection, is defined by the presence of more than 10, and up to 1,000 papular, acneiform and ulcerated lesions across at least two separate parts of the body (Turetz et al, 2002). While DCL patients exhibit poor lymphocyte proliferation and absent or low production of IFNg upon exposure to soluble leishmania antigen (SLA) (Petersen et al, 1984; Christensen et al, 2019), an impaired Th1 immune response has not been documented in DL (Machado et al, 2011). (V.) braziliensis-infected mice were found to occur independently from parasite burden, instead being directly associated with the presence of CD8 (+) T cells (Novais et al, 2013) Disease progression and metastasis in L. (V.) braziliensis-infected mice were found to occur independently from parasite burden, instead being directly associated with the presence of CD8 (+) T cells (Novais et al, 2013)

Methods

Results

Conclusion