HIV HIV / / T. gondii T. gondii co-infected co-infected patients patients produce lower produce lower levels of IFN-γ levels of IFN-γ in response to in response to T. gondii T. gondii antigens, antigens, even in the early stage of viral even in the early stage of viral infection infection E. Escobar, M. Alfonzo, M. Fernández, J. E. Escobar, M. Alfonzo, M. Fernández, J. Camacho, Y. Roldán, B. Alarcón de Noya, Camacho, Y. Roldán, B. Alarcón de Noya, M.E. de Quesada M.E. de Quesada UCV UCV / / IVIC IVIC Venezuela Venezuela eescobar@ivic. ve WELBA104
produce lower levels of IFN-γ produce lower levels of IFN-γ in response to in response to T. gondiiT. gondii antigens, antigens,
even in the early stage of viral infectioneven in the early stage of viral infection
E. Escobar, M. Alfonzo, M. Fernández, J. Camacho, E. Escobar, M. Alfonzo, M. Fernández, J. Camacho, Y. Roldán, B. Alarcón de Noya, M.E. de QuesadaY. Roldán, B. Alarcón de Noya, M.E. de Quesada
• HIV: Neurotropic and NeuropathicHIV: Neurotropic and Neuropathic– Mild DisturbanceMild Disturbance• FatigueFatigue• Sensitive / Cognitive ImpairmentSensitive / Cognitive Impairment• Motor DysfunctionMotor Dysfunction• Behavioral ChangeBehavioral Change
– Severe AffectionSevere Affection• HIV-Associated DementiaHIV-Associated Dementia
T. gondii T. gondii InfectionInfection
• Asymptomatic in Immunocompetent Hosts Asymptomatic in Immunocompetent Hosts – Tissue CystsTissue Cysts• Central Nervous SystemCentral Nervous System• Cardiac MuscleCardiac Muscle• EyeEye
• Reactivates in Immunodeficient HostsReactivates in Immunodeficient Hosts– Toxoplasmic EncephalitisToxoplasmic Encephalitis– CardiopathyCardiopathy– ChorioretinitisChorioretinitis
CoinfectionCoinfectionHIV HIV // Toxoplasma gondiiToxoplasma gondii
T. gondiiT. gondii Stage Interconversion Stage Interconversion
TachyzoiteTachyzoite BradyzoiteBradyzoite
Cellular StressCellular Stress•Heat ShockHeat Shock•Presence of Nitric OxidePresence of Nitric Oxide•Mitochondrial InhibitionMitochondrial Inhibition•Extreme pH Extreme pH (Low/High)(Low/High)
ImmunodeficiencyImmunodeficiency•Lack of T CellsLack of T Cells•Lack of IL-12, IFN-Lack of IL-12, IFN-γγ, , TNF-TNF-αα•Lack of Nitric OxideLack of Nitric Oxide
ControlControl
ReactivationReactivation
Trends in Parasitology 2002; 16(5):198-201.
ObjetiveObjetive
• Evaluate anti-Evaluate anti-T. gondiiT. gondii specific immune specific immune response in HIVresponse in HIV//T. gondiiT. gondii coinfected coinfected patientspatients**
* Several stages of viral infection* Several stages of viral infection
* No HAART nor anti-* No HAART nor anti-T. gondiiT. gondii treatment treatment
– In vitroIn vitro production of IFN-γ and TNF-α under production of IFN-γ and TNF-α under parasitic stimulation was assessed.parasitic stimulation was assessed.
Patients and Control GroupsPatients and Control Groups
IFN-γ and TNF-αIFN-γ and TNF-α Production Production under SATg stimulationunder SATg stimulation
• Coinfected Patients (P2) higher than P1Coinfected Patients (P2) higher than P1
• Coinfected Patients Lower than ControlsCoinfected Patients Lower than Controls
• Coinfected Patients Affected from early Coinfected Patients Affected from early stagesstages
ConclusionsConclusions
• Defects in IFN-γ (and TNF-α) production Defects in IFN-γ (and TNF-α) production in response to in response to Toxoplasma gondiiToxoplasma gondii may may impair anti-parasitic response in impair anti-parasitic response in coinfected patients since early stages of coinfected patients since early stages of viral infection viral infection
of brain parasitic latent infection may of brain parasitic latent infection may contribute to develop neurological signs contribute to develop neurological signs and symptoms even before toxoplasmic and symptoms even before toxoplasmic encephalitis appears.encephalitis appears.
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