TY - JOUR
T1 - IL-1R and inflammasomes mediate early pulmonary protective mechanisms in respiratory brucella abortus infection
AU - Hielpos, M. Soledad
AU - Fernández, Andrea G.
AU - Falivene, Juliana
AU - Paiva, Iván M.Alonso
AU - González, Florencia Muñoz
AU - Ferrero, Mariana C.
AU - Campos, Priscila C.
AU - Vieira, Angelica T.
AU - Oliveira, Sergio Costa
AU - Baldi, Pablo C.
N1 - Publisher Copyright:
© 2018 Hielpos, Fernández, Falivene, Alonso Paiva, Muñoz González, Ferrero, Campos, Vieira, Oliveira and Baldi.
PY - 2018
Y1 - 2018
N2 - Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1b and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.
AB - Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1b and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.
KW - Brucella abortus
KW - IL-1b
KW - Inflammasomes
KW - Innate immunity
KW - Respiratory infection
UR - http://www.scopus.com/inward/record.url?scp=85056730994&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056730994&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2018.00391
DO - 10.3389/fcimb.2018.00391
M3 - Article
C2 - 30456207
AN - SCOPUS:85056730994
SN - 2235-2988
VL - 8
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 391
ER -