TLR2, TLR4 and TLR9 are differentially modulated in liver lethally injured from BALB/c and C57BL/6 mice during Trypanosoma cruzi acute infection.
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.
Inmunologia, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, CIBICI-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
Eugenio Antonio
EA
Carrera-Silva
Carrera-Silva
CS
Eugenio Antonio
Roxana Carolina
RC
Cano
Cano Roxana
CR
Carolina
Natalia
N
Guiñazú
Guiñazu
G
Natalia
Maria Pilar
MP
Aoki
Aoki Maria
AM
Pilar
Andrea
A
Pellegrini
Pellegrini
P
Andrea
Susana
S
Gea
Gea
G
Susana
D000818:Animals; D014355:Chagas Disease / Q000235:genetics* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000469:parasitology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology
D018836:Inflammation Mediators; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9