CHARACTERIZATION OF INNATE IMMUNE RESPONSE IN A MURINE MODEL OF INTRATRACHEAL INFECTION WITH B. ABORTUS 2308

FOSSATI, CARLOS ALBERTO; BALDI, PABLO CÉSAR; BONETTO, JOSEFINA; FERRERO, MARIANA CRISTINA; FERNÁNDEZ, ANDREA GISELLE; HIELPOS, MARÍA SOLEDAD

Mar del Plata

Congreso; LX Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

CHARACTERIZATION OF INNATE IMMUNE RESPONSEIN A MURINE MODEL OF INTRATRACHEALINFECTION WITH B. ABORTUS 2308Hielpos, María Soledad1; Ferrero, Mariana Cristina1; Fernández,Andrea Giselle1; Bonetto, Josefina1; Fossati, CarlosAlberto1; Comerci, Diego J2; Baldi, Pablo C1Instituto de Estudios de la Inmunidad Homoral (IDEHU)-CONICET-UBA1 Instituto de Investigaciones Biotecnológicas(IIB), UNSAM-CONICET2Brucella is a human pathogen that can be acquired by inhalation.We studied the early stages of infection in a murine model of intratrachealinoculation in terms of bacterial dissemination and cytokine/chemokine response. Balb/c mice were inoculated at 106 or 104 CFUof B. abortus per animal. Lung, liver and spleen homogenates wereobtained at 1, 2, 3 and 7 days post infection (pi) and were usedfor CFU counting and for measuring cytokine and chemokines byELISA. We found that at 2h pi 77% of the inoculum remains in thelung. During the first 2 days pi, pulmonary bacterial counts in micereceiving the high inoculum dropped from 7.8 to 1.5 (x106) CFU.With the small inoculum, CFU remained constant around 12000CFU/lung for 4 days pi but increased at day 7 pi. CFU in spleens andlivers mimicked the kinetics in lungs, but started at 100 CFU/organwhen infected with 106 CFU; and were non-detectable until day 7pi with the lower inoculum (when they reached 100 CFU/organ).We measured IL-1β, TNF-α, KC, IL-10, IL-12 and MCP-1 in totallung homogenates. We found no significant differences betweencontrols and infected animals when inoculated with 104 CFU at anygiven time point. When we assessed the high inoculum group thetotal lung levels of MCP-1 and IL-1β increased significantly onlyafter 3 days pi (p<0.05), while KC and IL-12 increased at 7 days pi(p<0.05). TNF-α levels were lower in infected mice than in controlsat days 2 and 3 pi (p<0.01), and IL-10 levels followed the same pattern.In another set of experiments, mice inoculated intratracheallywith B. abortus or PBS received E. coli LPS through the same route1 day later, and lungs were harvested for histopathology 24 h later.A marked decrease in signs of inflammation was noted in lungs ofanimals from the Brucella/LPS group as compared with the PBS/LPS group. Our results show that B. abortus infection produces adelayed innate response in the lung and seems to subvert the localinflammatory response to PAMPs.