Contribution of inflammasomes to the control of the Respiratory Infection by Brucella spp.

FERNÁNDEZ, ANDREA GISELLE; HIELPOS, MARÍA SOLEDAD; FALIVENE JULIANA; FERRERO, MARIANA CRISTINA; COSTA OLIVEIRA SERGIO; BALDI, PABLO CÉSAR

Mar del Plata

Congreso; LXIV Reunión anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología

Contributionof inflammasomes to the control of the Respiratory Infection by Brucella spp. 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 the control of airborne B. abortus infection, IL-1 receptorknock-out mice(IL-1R KO) and wild type(WT) controls (C57BL/6 mice)were infected by the intra-trachealroute, 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 (neutrophilschemoattractant) were significantly lower in IL-1R KO mice at 7 days p.i. (88.3vs. 146.2 pg/ml, p<0.05). To determinewhether inflammasomes contribute 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.