CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TNF-BLOCKADE IN B CELL-DEFICIENT MICE INFECTED WITH TRYPANOSOMA CRUZI EXACERBATES A SYSTEMIC INFLAMMATORY RESPONSE AND INCREASES SUSCEPTIBILITY TO INFECTION Gorosito Serrán, Melisa ; Bermejo, Daniela ; Tosello-Boari, Jimena; Ramello, María Cecilia ; Amezc
Autor/es:
GOROSITO SERRAN, MELISA; BERMEJO, DANIELA A; TOSELLO BOARI, JIMENA; RAMELLO, MARIA CECILIA; AMEZCUA VESELY, MARIA CAROLINA; MONTES, CAROLINA LUCIA; ACOSTA RODRIGUEZ E V; GRUPPI, ADRIANA
Lugar:
Los Cocos
Reunión:
Jornada; LXI Reunión Anual de la sociedad argentina de Inmunología .; 2013
Institución organizadora:
Sociedad Argentina de Inmunologia
Resumen:
TNF-BLOCKADE IN B CELL-DEFICIENT MICE INFECTED WITH TRYPANOSOMA CRUZI
EXACERBATES A SYSTEMIC INFLAMMATORY RESPONSE AND INCREASES SUSCEPTIBILITY TO
INFECTION
Gorosito
Serrán, Melisa ; Bermejo,
Daniela ; Tosello-Boari, Jimena; Ramello, María Cecilia ; Amezcua-Vesely, María
Carolina; Montes, Carolina Lucía ; Acosta-Rodriguez, Eva Virginia ; Gruppi,
Adriana; CIBICI, CONICET - Facultad de Ciencias Químicas, UNC
B cell-deficient mice (C129.BL6uMT) (uMT) infected with T. cruzi Y-br
strain were more susceptible to the infection than control C57BL/6 mice (WT) as
70 % of infected uMT died after day 22 post-infection (d22pi), while 100% of WT
control survived. Considering that 30% of uMT infected mice survived to
the infection, we classified uMT infected mice in susceptible (who died before
d22pi) and resistant (who survived as WT).
We found that serum TNF in susceptible uMT was higher than WT?s, whereas
in resistant uMT TNF concentration was similar to WT?s. In order to evaluate
the role of TNF in uMT infected mice, uMT intraperitoneally infected with 10000
trypomastigotes were injected, since d13pi, with anti TNF-specific Rat IgG1
(TuMT) (1.5 mg/week) or with control Rat IgG (CuMT). Anti-TNF treated mice
recovered the 100% of their weight lost after starting treatment, but
surprisingly had a dramatic loss before dying, while CuMT lost a 20% of their
weight and kept only their 80% (WT=100% d0-30pi). We observed that TuMT mice
presented increased mortality (60% of TuMT and 100% of CuMT and WT mice
survived by d30pi). TuMT mice had higher concentrations of serum TNF, IFNg, and
IL12 (determined by quantitative ELISA) than CuMT and WT mice on d21 and d28pi
(p<0.001), increased levels of GPT than CuMT mice on d28pi (p<0.05) and
similar levels of glucose and GOT (d21 and d28pi). Interestingly, anti-TNF
treated mice presented similar tissue parasitism (determined by qRT-PCR) to
CuMT mice on day 21pi, but diminished on d28pi (p<0.05).
Our results suggest that TNF may be responsible for cachexia observed in
infected uMT mice, because the TNF blockade induces regaining of weight.
However, the treatment was unable to improve mice survival, probably because it
induces a pro-inflammatory response which may damage the liver, causing mice
death, and not due to uncontrolled parasitism. Additionally, this work may
reveal a negative loop by TNF regulating IL12 and IFNg-production.