Pulmonary inflammatory response subversion by Brucella abortus

HIELPOS, MS; FERRERO, MC; MUÑOZ GONZALEZ, FLORENCIA; FERNANDEZ, AG; FOSSATI CA,; COMERCI, DIEGO; BALDI, PC

Buenos Aires

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología, IV LASID Meeting, y II French-Argentinean Immunology Meeting; 2015

Sociedad Argentina de Inmunología y Sociedad Francesa de Inmunología

Introduction: Whereas Brucellainfections can be acquired through inhalation, lung inflammatory signs are mildor absent. We studied in mice the innate immune response in lung afterintratracheal (i.t.) infection, and a potential bacterial mechanism to subvertit.Methods: Balb/c mice were infected i.t. with wild type B.abortus (WT) or a double mutant for BtpA and BtpB proteins known to interferewith TLR signaling (btpA/btpB-); a control group received PBS. One day latersome animals were stimulated i.t. with LPS or peptidoglycan (PGN) fromEscherichia coli. Mice were euthanized at days 1, 2 and 7 to obtain lungs andspleens. Additionally, alveolar macrophages (AM) and pneumocytes fromnon-infected Balb/c mice were infected in vitro with both Brucella strains tomeasure cytokine responses.Results: Pulmonary inflammatory signs were mild in WT-infectedmice but were more pronounced in animals infected with btpAbtpB-. Nosignificant differences in pulmonary CFU counts were observed betweenbtpA/btpB- and WT infections, but spleen CFU counts were lower for the mutant. Inflammatorysigns were markedly reduced in lungs from the WT/LPS or WT/PGN groups ascompared with the PBS/LPS or PBS/PGN groups. The btpAbtpB-/LPS andbtpAbtpB-/PGN groups showed inflammation levels intermediate between thecorresponding WT and PBS groups. In vitroIL-1beta secretion by AM was higher in response to btpBbtpA- than in responseto WT, and the same was true for KC secretion by pneumocytes. Conclusions: Our results show that Btp proteins from B. abortus canmodulate the pulmonary inflammatory response to this bacterium or TLR agonists.