PULMONARY INFLAMMATORY RESPONSE SUBVERTION BY BRUCELLA ABORTUS

HIELPOS, M. SOLEDAD; FERRERO, MARIANA C.; MUÑOZ GONZÁLEZ, FLORENCIA; ANDREA G. FERNANDEZ; FOSSATI, C. ALBERTO; COMERCI, DIEGO; BALDI, PABLO C.

CABA, Buenos Aires

Congreso; I Meeting LASID-FAIC-SAI; 2015

LASID, FAIC & SAI

Introduction: Whereas Brucella infections can be acquired through inhalation, lunginflammatory signs are mild or absent. We studied in mice the innate immune response in lung afterintratracheal (i.t.) infection, and a potential bacterial mechanism to subvert it.Methods: Balb/c mice were infected i.t. with wild type B. abortus (WT) or a double mutant for BtpA andBtpB proteins known to interfere with TLR signaling (btpA/btpB-); a control group received PBS. Oneday later some animals were stimulated i.t. with LPS or peptidoglycan (PGN) from Escherichia coli. Micewere euthanized at days 1, 2 and 7 to obtain lungs and spleens. Additionally, alveolar macrophages(AM) and pneumocytes from non-infected Balb/c mice were infected in vitro with both Brucella strains tomeasure cytokine responses.Results: Pulmonary inflammatory signs were mild in WT-infected mice but were more pronounced inanimals infected with btpAbtpB-. No significant differences in pulmonary CFU counts were observedbetween btpA/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 as compared with thePBS/LPS or PBS/PGN groups. The btpAbtpB-/LPS and btpAbtpB-/PGN groups showed inflammationlevels intermediate between the corresponding WT and PBS groups. In vitro IL-1beta secretion by AMwas higher in response to btpBbtpA- than in response to WT, and the same was true for KC secretionby pneumocytes. Conclusions: Our results show that Btp proteins from B. abortus modulate the pulmonary inflammatoryresponse to this bacterium or TLR agonists.