Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil

Author(s):Show less -

da Matta, Vania Lucia R. ; Goncalves, Andre N. ; Gomes, Claudia Maria C. ; Chouman, Islam H. ; Ferreira, Frederico M. ; Campos, Marliane B. ; Lima, Luciana V. ; dos Santos, Thiago Vasconcelos ; Ramos, Patricia Karla ; Furtado, Rodrigo R. ; Laurenti, Marcia D. ; Corbett, Carlos Eduardo P. ; Nakaya, Helder I. ; Silveira, Fernando T.

• Document type: Journal article
• Source: MICROORGANISMS; v. 11, n. 3, p. 14-pg., 2023-03-01.

Abstract

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical-immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Para State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical-immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon. (AU)

• FAPESP's process: 14/50315-0 - Leishmaniasis in Latin America: an advanced perspective on immunopathogenetic factors of cutaneous and visceral infection, immunomodulators of the sandflies vector saliva and immunogenic exo-antigens of Leishmania (L.) infantum chagasi as vaccine candidates
• Grantee: Marcia Dalastra Laurenti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/02626-8 - Nitric oxide and reactive species of oxygen evaluation in human infection caused by Leishmania (L.) infantum chagasi
• Grantee: Islam Hussein Chouman
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training