Role of inflammasomes in the control of B. abortus airway infection in mice

HIELPOS, MS; COSTA-OLIVEIRA, S; FERNANDEZ, AG; FALIVENE, J; FERRERO, MC; BALDI, PC

Buenos Aires

Congreso; III International Congress on Translational Medicine; 2016

Facultad de Farmacia y Bioquímica UBA

Inhalationof infected aerosols is one of the most frequent routes for acquiring Brucella spp. infection. The role of IL-1βand inflammasome activation in the initial control of this infection has notbeen studied. To determine whether pulmonary IL-1β contributes to thecontrol of airborne B. abortus infection,IL-1 receptorknock-outmice(IL-1R KO) and wild type (WT) controls (C57BL/6 mice)were infected by the intra-tracheal route, and lung CFU were measured at 2 and 7 days p.i. While no significant difference was found at 2 daysp.i., CFU counts were significantly higher in IL-1R KO mice at 7 days p.i. ascompared to WT (mean, 3.15 x 107 vs. 1.12 x 106 CFU;p<0.01).Pulmonary levels of KC (neutrophils chemoattractant)were significantly lower in IL-1R KO mice at 7 days p.i. (88.3 vs. 146.2 pg/ml,p<0.05). To determine whether inflammasomescontribute to the control of airborne B.abortus infection, KO mice for caspase-1 (Casp-1), NRLP3 or AIM2 were infected by the intra-tracheal route, and lung CFU andcytokines were measured at different p.i. times.CFU counts were higher inCasp-1, NLRP3 and AIM2 KO mice (8.01 x 106, 1.18 x 107,and 5.43 x 106 CFU/ml, respectively)as compared to WT (0.81 x 106CFU/ml), although differences only reached statistical significance for NLRP3(p<0.01). In addition, at 2 days p.i. levels of IL-1βwere lower in Casp-1 KOmice than in WT (213 vs. 465 pg/ml, p<0.01), and the same was true for KC(96 vs. 157 pg/ml, p<0.01), IL-12 (73 vs. 295 pg/ml, p<0.05) and TNF-α(130 vs. 260 pg/ml, p<0.001). To determine the role of different lung cellsin these responses, alveolar macrophages and pneumocytes were obtained from WTmice and were infected in vitro in the presence or absence of a Casp-1 inhibitor (Z-WEHD-FMK). For both cell types, IL-1βlevels were significantly lower in the presence of the inhibitor. These results show that inflammasomes playan important role in the initial control of Brucellainfection acquired through the airways.