Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human Leishmania (L.) infantum chagasi Infection.

Patrícia Karla Ramos,Daniela Santoro Rosa,Fernando Tobias Silveira,Márcia Dalastra Laurenti,Marliane Batista Campos,Carlos Eduardo Corbett,Luciana Vieira Lima,Karina Inácio Carvalho,Ana Paula Rodrigues,Claudia Maria C Gomes

doi:10.1155/2016/6937980

Abstract

The clinical-immunological spectrum of human Leishmania (L.) infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG) evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III) and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI). TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases), III (49), SRI (19), SOI (12), AI (36), and a control group [CG] (24). The highest IL-6 serum levels were observed in the SI profile (AVL); higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.

Highlights

American visceral leishmaniasis (AVL) is considered the major clinical feature of Leishmania (L.) infantum chagasi and human immune response, there is no doubt that additional clinical-immunological features resulting from this interaction could contribute to better understanding the entire immune response to infection
Higher IL-6 serum levels were found in the Susceptible immune response infection (SI) profile (AVL) in the first analysis as compared to the other profiles; significantly higher IL-10 serum levels were observed in the SI profile (AVL) as compared to the subclinical oligosymptomatic infection (SOI) and the control group (CG) and in the asymptomatic infection (AI) and initial infection (III) profiles as compared to the SOI
Significantly higher TNF-α serum levels were detected in the SI profile (AVL) as compared to CG and in the AI profile as compared to the III

Summary

Introduction

American visceral leishmaniasis (AVL) is considered the major clinical feature of Leishmania (L.) infantum chagasi and human immune response, there is no doubt that additional clinical-immunological features resulting from this interaction could contribute to better understanding the entire immune response to infection. Chagasi infection in Para State, Amazonian Brazil, based on the combined use of the semiquantitative delayed-type hypersensitivity (DTH) and indirect fluorescent antibody tests (IFAT-IgG) have confirmed their ability to diagnose either asymptomatic or symptomatic infections in endemic areas [1]. Chagasi antigens, promastigotes for DTH, and amastigotes for IFAT (IgG), associated with the clinical status of the infected individuals, has allowed the identification of a wide infection spectrum composed of five clinical-immunological profiles: three asymptomatic, (1) asymptomatic infection (AI) [DTH+/++++, IFAT−], (2) subclinical resistant infection (SRI) [DTH+/++++, IFAT+/++], and (3) indeterminate initial infection (III) [DTH−, IFAT+/++] and two symptomatic, (4) symptomatic. Symptomatic infection (SI = AVL) LST − IFAT +++/++++. Asymptomatic infection (AI) LST +/++++ IFAT − The high specificity of this diagnostic approach using species-specific L. (L.) i. chagasi antigens, promastigotes for DTH, and amastigotes for IFAT (IgG), associated with the clinical status of the infected individuals, has allowed the identification of a wide infection spectrum composed of five clinical-immunological profiles: three asymptomatic, (1) asymptomatic infection (AI) [DTH+/++++, IFAT−], (2) subclinical resistant infection (SRI) [DTH+/++++, IFAT+/++], and (3) indeterminate initial infection (III) [DTH−, IFAT+/++] and two symptomatic, (4) symptomatic

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Conclusion