Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Abstract

BackgroundHIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed.Case presentationA 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+ T cells and higher percentage of activated CD4+ T cells at HAART initiation. The percentage of memory CD4+ T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+ T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset.ConclusionAlthough both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2159-x) contains supplementary material, which is available to authorized users.

CD4 + T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis

“…Thus, future T cell-targeted therapies for patients with severe cryptococcal CNS disease will need to identify critical windows of T cell functions and carefully weigh their pathological versus beneficial effects. These data showing the pathological potential of IFN-␥-producing T cells in the CNS during C. neoformans meningoencephalitis are supported by notable damaging roles of CD4 ϩ and CD8 ϩ T cells in the CNS during infections, including cerebral malaria (63)(64)(65), viral encephalitis (66), toxoplasmosis (67)(68)(69), tuberculosis meningitis (27), and immunological disorders such as multiple sclerosis (70). However, a similar paradigm exalting paradoxical roles for T cells has only recently begun to emerge in the study of cryptococcal infections.…”

Chemokine receptor CXCR3 is required for lethal brain pathology but not pathogen clearance during cryptococcal meningoencephalitis

“…Cumulatively, these studies and our current data highlight the contribution of the CXCR3/CXCL10 axis to a spectrum of inflammatory diseases, including those affecting the CNS. The role of this pathway continues to be investigated in other neurological diseases in which CD4 + T cells and CD8 + T cells inflict damage, including viral encephalitis (53,54), cerebral toxoplasmosis (55,56), and cerebral tuberculosis (6,57).…”

Strain- and Dose-Dependent Reduction of Toxoplasma gondii Burden in Pigs Is Associated with Interferon-Gamma Production by CD8+ Lymphocytes in a Heterologous Challenge Model

“…As recently shown in mice, the robust immune reaction expressed by the high IFN-γ levels in the acute phase of the infection severely reduces the activity of Tregs in a IL-2 dependent and IL-10 independent manner (Tenorio et al, 2011 ; Olguin et al, 2015 ). In a longitudinal clinical case study of human acquired cerebral toxoplasmosis a dual function of the Treg population was described, by simultaneous down regulation of CD4 + and activation of pathogen-specific CD8 + T lymphocytes (Rb-Silva et al, 2017 ). In human congenital infections not only CD4 + Treg cell population seems to be involved in the immune reaction triggered by T. gondii , but also a different subset of CD4 + or CD8 + , namely Th17.…”