HIVT' gondii coinfected patients produce lower levels of IFN in response to T' gondii antigens, even

1
HIV/T. gondii co-infected patients produce lower
levels of IFN-? 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

eescobar_at_ivic.ve WELBA104
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HIV InfectionCentral Nervous System

• HIV Neurotropic and Neuropathic
• Mild Disturbance
• Fatigue
• Sensitive / Cognitive Impairment
• Motor Dysfunction
• Behavioral Change
• Severe Affection
• HIV-Associated Dementia

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T. gondii Infection

• Asymptomatic in Immunocompetent Hosts
• Tissue Cysts
• Central Nervous System
• Cardiac Muscle
• Eye
• Reactivates in Immunodeficient Hosts
• Toxoplasmic Encephalitis
• Cardiopathy
• Chorioretinitis

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Coinfection

• HIV / Toxoplasma gondii

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T. gondii Stage Interconversion

• Cellular Stress
• Heat Shock
• Presence of Nitric Oxide
• Mitochondrial Inhibition
• Extreme pH (Low/High)

Control
Tachyzoite
Bradyzoite
Reactivation

• Immunodeficiency
• Lack of T Cells
• Lack of IL-12, IFN-?, TNF-a
• Lack of Nitric Oxide

Trends in Parasitology 2002 16(5)198-201.
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Objetive

• 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-? and TNF-a under
  parasitic stimulation was assessed.

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Patients and Control Groups
Controls
Patients
HIV (-)
HIV ()
C1 T. gondii (-)
C2 T. gondii ()
P1 T. gondii (-)
P2 T. gondii ()
A CD4 gt 350/ul
B CD4 200-350/ul
C CD4 lt200/ul
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Cell Culture
PBMC 1 x 105 cells 200 ul
SATg 1 ug/ml Soluble Antigens of T. gondii RH
strain
Medium Alone RPMI, 10 FCS
PHA 5 ug/ml
Culture 72 hours 37C, 5 CO2
Supernatants Citokine Determinations (Flow
cytometry-CBA, Becton-Dickinson)
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Results
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IFN-? Production
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IFN-? Production under SATg Stimulation
12
TNF-a Production
13
TNF-a Production under SATg Stimulation
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IFN-? and TNF-a Production under SATg stimulation

• Coinfected Patients (P2) higher than P1
• Coinfected Patients Lower than Controls
• Coinfected Patients Affected from early stages

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Conclusions

• Defects in IFN-? (and TNF-a) 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.

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Acknowledgments
Universidad Central de Venezuela

• Catedra de
• Microbiologia-
• Hospital Jose I. Baldo
• Yajhaira Roldan

• Laboratorio de
• Inmunofisiologia Celular
• Miguel Alfonzo
• Josibel Camacho
• Alexandra Diaz
• Riward Campello

• Laboratorio de
• Neurofisiologia
• Maria Esther de
• Quesada

• Instituto de
• Medicina Tropical
• Belkysiole Alarcon de
• Noya

FONACIT Ministerio de Ciencia y Tecnologia
Instituto Venezolano de Investigaciones
Cientificas

• Laboratorio de
• Fisiopatologia
• Mercedes Fernandez

• Grant
• PhD Fellowship