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

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

Ciudad Autónoma de Buenos Aires

Congreso; III International Congress in Translational Medicine; 2016

International Master Program in Biomedical Sciences (IMBS) / Universidad de Buenos Aires (Argentina) - Albert-Ludwigs University of Freiburg (Germany)

Inhalation of infected aerosols is one of themost frequent routes for acquiring Brucellaspp. infection. The role of IL-1β and inflammasome activation in the initialcontrol of this infection has not been studied. To determine whether pulmonary IL-1β contributes to the control of airborne B. abortus infection, IL-1 receptor knock-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 (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 in Casp-1, NLRP3 and AIM2 KO mice (8.01 x 106,1.18 x 107, and 5.43 x 106 CFU/ml, respectively) ascompared to WT (0.81 x 106 CFU/ml), although differences onlyreached statistical significance for NLRP3 (p<0.01). In addition, at 2 daysp.i. levels of IL-1β were lower in Casp-1 KO mice 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 (73vs. 295 pg/ml, p<0.05) and TNF-α (130 vs. 260 pg/ml, p<0.001). Todetermine the role of different lung cells in these responses, alveolarmacrophages and pneumocytes were obtained from WT mice and were infected invitro in the presence or absence of a Casp-1inhibitor (Z-WEHD-FMK). For both cell types, IL-1β levels weresignificantly 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.