BACKGROUND: Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. METHODOLOGY/PRINCIPAL FINDINGS: Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. CONCLUSIONS/PRINCIPAL FINDINGS: Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.
BACKGROUND:Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. METHODOLOGY/PRINCIPAL FINDINGS: Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. CONCLUSIONS/PRINCIPAL FINDINGS: Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.
Authors: Gustavo F S Quirino; Manuela S L Nascimento; Marcela Davoli-Ferreira; Lais A Sacramento; Mikhael H F Lima; Roque P Almeida; Vanessa Carregaro; João Santana Silva Journal: Infect Immun Date: 2016-07-21 Impact factor: 3.441
Authors: Gabriela Freire Bezerra; Gdayllon Cavalcante Meneses; Vittória Nobre Jacinto; Danya Bandeira Lima; Emanuel Paula Magalhães; Lana Andrade Lucena Lima; Thaiany Pereira da Rocha; Isabella Evelyn Prado de Azevedo; Geraldo Bezerra da Silva; Elizabeth De Francesco Daher; Alice Maria Costa Martins Journal: Am J Trop Med Hyg Date: 2022-02-21 Impact factor: 2.345
Authors: Diego Lins Guedes; Elis Dionísio da Silva; Maria Carolina Accioly Brelaz Castro; Walter Lins Barbosa Júnior; Ana Victoria Ibarra-Meneses; Achilleas Tsoumanis; Wim Adriaensen; Johan van Griensven; Valéria Rêgo Alves Pereira; Zulma Maria de Medeiros Journal: PLoS Negl Trop Dis Date: 2022-06-17
Authors: Samuel R Aquino; Lucyo F B Diniz; Igor T Queiroz; Mirella A Cunha; Alda M Justo; Elis D Silva; Valéria R A Pereira; Zulma M Medeiros; Rodrigo F Carmo Journal: Am J Trop Med Hyg Date: 2020-09-03 Impact factor: 3.707