HIV/T. gondii co-infected patients produce lower levels of IFN-γ in response to T. gondii antigens, even in the early stage of viral infection E. Escobar, M. Alfonzo, M. Fernández, J. Camacho, Y. Roldán, B. Alarcón de Noya, M.E. de Quesada UCV / IVIC Venezuela WELBA104

HIV Infection Central Nervous System HIV: Neurotropic and NeuropathicHIV: Neurotropic and Neuropathic –Mild Disturbance FatigueFatigue Sensitive / Cognitive ImpairmentSensitive / Cognitive Impairment Motor DysfunctionMotor Dysfunction Behavioral ChangeBehavioral Change –Severe Affection HIV-Associated DementiaHIV-Associated Dementia

T. gondii Infection Asymptomatic in Immunocompetent HostsAsymptomatic in Immunocompetent Hosts –Tissue Cysts Central Nervous SystemCentral Nervous System Cardiac MuscleCardiac Muscle EyeEye Reactivates in Immunodeficient HostsReactivates in Immunodeficient Hosts –Toxoplasmic Encephalitis –Cardiopathy –Chorioretinitis

Coinfection HIV / Toxoplasma gondii

T. gondii Stage Interconversion TachyzoiteBradyzoite Cellular Stress Heat ShockHeat Shock Presence of Nitric OxidePresence of Nitric Oxide Mitochondrial InhibitionMitochondrial Inhibition Extreme pH (Low/High)Extreme pH (Low/High) Immunodeficiency Lack of T CellsLack of T Cells Lack of IL-12, IFN-γ, TNF-αLack of IL-12, IFN-γ, TNF-α Lack of Nitric OxideLack of Nitric Oxide Control Reactivation Trends in Parasitology 2002; 16(5):

Objetive Evaluate anti-T. gondii specific immune response in HIV/T. gondii coinfected patients*Evaluate anti-T. gondii specific immune response in HIV/T. gondii coinfected patients* * Several stages of viral infection * No HAART nor anti-T. gondii treatment –In vitro production of IFN-γ and TNF-α under parasitic stimulation was assessed.

Patients and Control Groups ControlsControlsPatientsPatients HIV (-) HIV (+) C1 T. gondii (-) C1 C2 T. gondii (+) C2 P1 T. gondii (-) P1 P2 T. gondii (+) P2 A CD4 > 350/ul A B CD /ul B C CD4 <200/ul C

Cell Culture PBMC 1 x 10 5 cells 200 ul PBMC 1 x 10 5 cells 200 ul Medium Alone RPMI, 10% FCS Medium Alone RPMI, 10% FCS PHA 5 ug/ml PHA SATg* 1 ug/ml *Soluble Antigens of T. gondii RH strain SATg* 1 ug/ml *Soluble Antigens of T. gondii RH strain Culture 72 hours 37°C, 5% CO 2 Culture 72 hours 37°C, 5% CO 2 Supernatants Citokine Determinations (Flow cytometry-CBA, Becton-Dickinson) Supernatants Citokine Determinations (Flow cytometry-CBA, Becton-Dickinson)

RESULTS

IFN-γ Production

IFN-γ Production under SATg Stimulation

TNF-α Production

TNF-α Production under SATg Stimulation

IFN-γ and TNF-α Production under 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 stagesCoinfected Patients Affected from early stages

Conclusions Defects in IFN-γ (and TNF-α) production in response to Toxoplasma gondii may impair anti-parasitic response in coinfected patients since early stages of viral infectionDefects in IFN-γ (and TNF-α) production in response to Toxoplasma gondii may impair anti-parasitic response in coinfected patients since early stages of viral infection Eventual reactivation (even partial / limited) of brain parasitic latent infection may contribute to develop neurological signs and symptoms even before toxoplasmic encephalitis appears.Eventual reactivation (even partial / limited) of brain parasitic latent infection may contribute to develop neurological signs and symptoms even before toxoplasmic encephalitis appears.