title: The innate immune response status correlates with a divergent clinical course in congenital Chagas disease of twins born in a non-endemic country.
abstract: The innate immune response from diamniotic and dichorionic twin brothers congenitally infected with Trypanosoma. cruzi (strain DTU-V) who displayed different clinical symptomatology was studied. While Brother I manifested severe cardiac and digestive disorders, the Brother II showed slight splenomegaly. The secretion level of IL-1β, TNF-α, IL-12, IL-10, IFN-α and IL-6 cytokines produced after stimulation of peripheral blood cells with TLR-2, TLR-4 and TLR-9 ligands was determined pre- and post-benznidazole treatment. Cells from 10 uninfected infants born to mothers seropositive for Chagas disease were included as control. The obtained data show that the cells of Brother I secreted lower levels of the pro-inflammatory cytokines IL-1β and TNF-α (upon TLR-2 and TLR-4 stimulation) relative to those secreted by cells from Brother II and uninfected controls. The cells from Brother II secreted high levels of the IL-1β cytokine following TLR-2 stimulation relative to uninfected controls. The cells from both brothers secreted a higher level of IL-6, following TLR-4 stimulation, than that secreted by uninfected infant cells. After treatments, the cytokine secretion levels were similar in both children and comparable to those of uninfected donors. Treatment success in Brother I and treatment interruption in Brother II was detected by the use of serological biomarkers (KMP11, HSP70, PFR2, Tgp63) as well as follow-up done by PCR. Therefore, the Brother II required a second treatment. The data presented suggest that benznidazol treatment allows the innate immune system to reach a fully functional status similar to that of uninfected subjects.
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Villegas
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: Unidad Regional de Medicina Tropical, Hospital Virgen de la Arrixaca, Cra. Cartagena s/n El Palmar, 30120 Murcia, Spain.
authors.forename: Bartolomé
authors.initials: B
authors.lastname: Carrilero
authors.affiliation: Unidad pediátrica de Cuidados Intensivos, Hospital Virgen de la Arrixaca, Cra. Cartagena s/n El Palmar, 30120 Murcia, Spain.
authors.forename: Cinta
authors.initials: C
authors.lastname: Téllez
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Marañón
authors.affiliation: Unidad Regional de Medicina Tropical, Hospital Virgen de la Arrixaca, Cra. Cartagena s/n El Palmar, 30120 Murcia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Murcia
authors.affiliation: Unidad pediátrica de Cuidados Intensivos, Hospital Virgen de la Arrixaca, Cra. Cartagena s/n El Palmar, 30120 Murcia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Moralo
authors.affiliation: Centro de Biología Molecular Severo-Ochoa, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Unidad Regional de Medicina Tropical, Hospital Virgen de la Arrixaca, Cra. Cartagena s/n El Palmar, 30120 Murcia, Spain. Electronic address: msegovia@um.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Segovia
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18016 Granada, Spain. Electronic address: mclopez@ipb.csic.es.
authors.forename: Manuel Carlos
authors.initials: MC
authors.lastname: López
mesh_terms: D000328:Adult; D014355:Chagas Disease / Q000151:congenital / Q000188:drug therapy / Q000276:immunology* / Q000635:transmission; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004200:Diseases in Twins / Q000151:congenital / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009593:Nitroimidazoles / Q000008:administration & dosage*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology; D013030:Spain; D014344:Trypanocidal Agents / Q000008:administration & dosage*; D014429:Twins, Dizygotic
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole
keywords: Chagas disease; Congenital transmission; Innate immune response; PCR; Serological biomarker; Trypanosoma cruzi