Page 111 - Resúmen - XXV Congreso Latinoamericano de Parasitología - FLAP

S4-01

Clinical, immunological and genetic characteristics of the spectrum of

human L. (L.) infantum infection in the Brazilian Amazon.

Vânia Lucia R. da Matta , Rodrigo R. Furtado , Andre Nicolau A. Gonçalves , Helder T. I.
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Nakaya , Claudia Maria C. Gomes , Marcia D. Laurenti , Carlos Eduardo P. Corbett ,
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Fernando T. Silveira .
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1 Faculdade de Medicina da Universidade de São Paulo, Instituto Evandro Chagas, Faculdade de
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Ciências Farmacêuticas da Universidade de São Paulo
We demonstrated a clinical-immunological spectrum of human infection caused by Leishmania (L.)
infantum in endemic areas of American visceral leishmaniasis (AVL) in the Brazilian Amazon. This
spectrum, which was based on the specific antibody levels, response to leishmanin skin test, and
absence/presence of clinical manifestations, comprises the indeterminate initial infection (III), asymptomatic
infection (AI), subclinical resistant infection (SRI), oligosymptomatic subclinical infection (SOI), and
symptomatic infection (AVL). Prospective studies indicated that the infection evolves from III profile to either
the resistant profiles (SRI and AI) or to the susceptible ones (AVL and SOI).Thus, it is of great interest to
clarify the immunopathogenetic basis that support these sequences of clinical-immunological events,
leading to susceptibility or resistance to infection, which may support new strategies for the control and
treatment of AVL. In this direction, we analyzed the transcriptome of 48 individuals from the five clinical-
immunological groups (III n=15, AI n=15, SRI n=7, SOI n=3, AVL n=2), and negative controls (n=6). After
global sequencing of mRNA (RNAseq) on the Illumina platform, we performed the mapping against the
human reference genome (GRCh38 version), automatic annotation and quantification of gene expression.
The differential gene expression (DEGs) were obtained using the edgeR tool. Results: i- Susceptible pole
(AVL) showed more DEGs than the resistant pole (AI) in relation to negative (healthy) controls for both up-
regulated genes (1.011 DEGs in AVL and 363 DEGs in AI) and down-regulated genes (582 DEGs in AVL
and 159 DEGs in AI), ii- AVL and AI groups shared 144 DEGs with increased activity, such as the
neutrophil-mediated immunity pathways and the hydrogen peroxide catabolic/metabolic process, indicating
central functions of these pathways in L. (L.) infantum infection, iii-conversely, specific signatures for AVL
presented enrichment for some pathways, including those that regulate complement activation, humoral
response and acute inflammation, while cytokine-mediated signaling pathways and cellular response to
cytokine stimulus were signatures of asymptomatic individuals (AI); iv- comparative analysis of gene
expression of other clinical-immunological profiles with negative controls showed up-regulation of
phagocytosis in profile III, down-regulation in neutrophil degranulation pathways in SRI and down regulation
of classic complement pathway activation in SOI. Conclusions: This initial study of gene expression
showed that individuals infected with L. (L.) infantum who manifest disease (AVL) have higher number of
DEGs compared to AI, indicating more transcriptional activity in the disease. We also showed specific
signatures for symptomatic and asymptomatic infection, as well as a core of activated genes/pathways
shared by the two groups, indicating central functions of such genes/pathways in parasite infection. In
addition, we identified down, or up regulation of genes related to innate and acquired immune response in
profiles III, SOI, and SRI. Finally, we believe that the complete transcriptome study will enable the
identification of transcriptomic factors related to the evolution of individuals from initial infection (III) to the
resistant or susceptible profiles, which could support new strategies of treatment and control of AVL.

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