Cerebral and ocular toxoplasmosis related with IFN-γ, TNF-α, and IL-10 levels.

Gabriela Motoie,Luiz C. de Mattos,Cristina S. Meira,Ricardo Gava,Cinara C. Brandão de Mattos,Thais A. Costa-Silva,Fábio B. Frederico,José E. Vidal,Vera L. Pereira-Chioccola

doi:10.3389/fmicb.2014.00492

Abstract

This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT/AIDS patients produced low levels of IL-10 (Th2 response) and IFN-γ (Th1 response). They produced high TNF-α suggesting a high inflammatory response triggered by the parasite.

Highlights

Lifelong infection with the obligate intracellular protozoan Toxoplasma gondii affects one-third of the human population globally (Weiss and Dubey, 2009)
2564.01 (21.12–11253.62) 2352.00 aCT, OT. bDate of the collection. c Diagnosis was defined by clinical, images and laboratory data as described in Materials and Methods Section. d Active and retinochoroiditis (RtC) scars in the right and left eyes, respectively. eNon-determined (ND). f Number of CD4+ T lymphocytes/μl of blood. g ELISA are expressed in relative values (RV), which represent the ratio of the absorbance of each serum sample at an optical density of 492 nm to the cutoff value
No differences in Interleukin 10 (IL-10) levels were observed between peripheral blood mononuclear cells (PBMC) collected from CHR individuals and CT/AIDS or OT patients (466.80 pg/mL, 311.50 pg/mL and 580.60 pg/mL, respectively)

Summary

Introduction

Lifelong infection with the obligate intracellular protozoan Toxoplasma gondii affects one-third of the human population globally (Weiss and Dubey, 2009). Toxoplasmosis is asymptomatic in the majority of cases, T. gondii infection can have serious consequences in immunocompromised individuals and in cases of congenital infection. In the latter case, ocular infection, posterior retinochoroiditis, is the most frequent clinical manifestation of congenital and acquired toxoplasmosis (Delair et al, 2011; Olariu et al, 2011; Dubey et al, 2012). The severity and prevalence of the disease vary greatly and is believed to be affected by the status of the host immune system (Garweg and Candolfi, 2009), the genotype of infective parasite strains (Pereira-Chioccola et al, 2009; Dubey et al, 2012), and the host genetic background (Mack et al, 1999; Sullivan and Jeffers, 2012). Reactivation of the latent infection occurs in www.frontiersin.org

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