Short report
Resistance to visceral leishmaniasis is severely compromised in mice deficient of bradykinin B2-receptors
1 Instituto de Microbiologia Paulo de Góes, CCS, Universidade Federal do Rio de Janeiro (UFRJ), Avda. Carlos Chagas 373. Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Caixa Postal 68040, 21941-902, Brazil
2 Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, 21949-900, Brazil
3 Hospital Universitário Clementino Fraga Filho-Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, CEP 21941-913, Brazil
Parasites & Vectors 2012, 5:261 doi:10.1186/1756-3305-5-261
Published: 14 November 2012Abstract
Background
Kinins liberated from plasma–borne kininogens, are potent innate stimulatory signals. We evaluated whether resistance to infection by Leishmania (L.) chagasi depends on activation of G-protein coupled bradykinin B2 receptors (B2R).
Findings
B2R −/− C57BL/6 knock-out (KOB2) and B2R+/+ C57BL/6-wild type control mice (C57) were infected with amastigotes of Leishmania (L.) chagasi. Thirty days after infection, the KOB2 mice showed 14% and 32% relative increases of liver (p< 0.017) and spleen weights (p<0.050), respectively, whereas liver parasite load increased 65% (p< 0.011) in relation to wild type mice. The relative weight increases of liver and spleen and the parasite load were positively correlated (R = 0.6911; p< 0.007 to R = 0.7629; p< 0.001, respectively). Conversely, we found a negative correlation between the increased liver relative weight and the weakened DTH response (a strong correlate to protection or natural resistance to VL) or the decreased levels of IgG2b antibodies to leishmanial antigen. Finally, we also found that IFN-γ secretion by splenocytes, an adaptive response that was significantly decreased in KOB2 mice (p< 0.002), was (i) negatively correlated to the increase in liver LDU (R = −0.6684; p = 0.035) and liver/body relative weight (R = −0.6946; p = 0.026) and (ii) positively correlated to serum IgG2b levels (R = 0.8817; p = 0.001).
Conclusions
We found that mice lacking B2R display increased susceptibility to the infection by Leishmania (L.) chagasi. Our findings suggest that activation of the bradykinin/B2R pathway contributes to development of host resistance to visceral leishmaniasis.
