RESUMO
Toll-like receptor (TLR) family is crucial for microbial elimination and homeostasis, and has an important immunoregulatory role. In this study, we comparatively analyze innate immune response and tissular injury elicited in BALB/c and C57BL/6 (B6) mice during acute Trypanosoma cruzi infection. The liver was the most affected tissue with numerous cellular infiltrates, apoptotic cells and necrotic areas. The apoptotic rate, evaluated by Hoescht stain, was highest in liver of B6. Infection increased transaminase activities in both mouse strains, although they were highest in B6. BALB/c showed sixfold higher parasitemias than B6 but the latter presented higher mortality (80%) than BALB/c (40%). To gain insight into the molecular basis, we investigated the TLRs commitment in liver. We found that, TLR2 and TLR4 were up-regulated in BALB/c while they were down-regulated in B6. However, TLR9 showed a diminution in BALB/c and an increase in B6 at the end of infection. Moreover, an intensified pro-inflammatory cytokine profile was observed in B6 and F4/80+ and Gr1+ leukocytes were the predominant cells in liver from both mouse strains. Thus, altered TLR2, TLR4 and TLR9 signalling and exacerbate inflammatory cytokine profile could be responsible of the fatal hepatic damage observed in infected B6.
Assuntos
Doença de Chagas/genética , Fígado/metabolismo , Camundongos Endogâmicos BALB C/genética , Camundongos Endogâmicos C57BL/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genética , Animais , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Feminino , Regulação da Expressão Gênica , Coração/parasitologia , Mediadores da Inflamação/metabolismo , Fígado/parasitologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C/metabolismo , Camundongos Endogâmicos BALB C/parasitologia , Camundongos Endogâmicos C57BL/metabolismo , Camundongos Endogâmicos C57BL/parasitologia , Miocárdio/metabolismo , Miocárdio/patologia , Transdução de Sinais/genética , Baço/metabolismo , Baço/patologia , Análise de Sobrevida , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Trypanosoma cruzi/imunologiaRESUMO
OBJECTIVE: To describe auditory perceptual, pre-attentive, attention-related and cognitive processes along lifespan in normal people by a simple auditory oddball paradigm easily usable in clinical practice. METHODS: ERPs were recorded in 72 normal subjects. Four blocks of tones were delivered (20% rare 2,000 Hz and 80% frequent 1,000 Hz). In the former two blocks, subjects performed a concomitant distracting visual search task (distracted condition); in the latter two blocks, they had to attend the occurrence of the rare tones (active condition). Latency and amplitude of ERPs were analyzed according to age, gender, educational level and repetition. RESULTS: N100 amplitude was greater in active than in distracted condition. MMN amplitude decreased with age. N2b and P300 latencies increased with age, while their amplitudes decreased. Females produced greater P300 than males. In the elderly, P300 latency was found to be longer in the second block than in the first one. CONCLUSIONS: N100 and MMN were found to be less affected by age than N2b and P300. When repeated, P300 showed increased latency in elderly subjects. SIGNIFICANCE: The protocol detected the higher influence of aging on late cognitive processes than on the perceptual and pre-attentive ones. Age-adjusted normative data were produced.
