STAT1 and STAT2 signaling play a protective role against bacterial colonization and development of neurologic signs during Brucella infection 2464

Abstract Description Brucellosis is a globally significant zoonotic disease. Human brucellosis patients develop flu-like symptoms and focal complications including arthritis and neurobrucellosis. The purpose of our study was to uncover the role of interferons and STAT signaling in the development of neurobrucellosis. At multiple timepoints following intranasal infection of mice with Brucella melitensis, we found that STAT1-deficient animals (Stat1-/-) had elevated levels of Brucella in the brain, blood, lung and spleen when compared to wild-type (WT) mice or mice lacking the IFN-γ receptor (Ifngr1-/-). Stat1-/- mice also developed neurologic signs and became moribund at a higher rate when compared to Ifngr1-/- mice. We found that mice lacking both STAT1 and the receptor for IFN-y (STAT1-/-/Ifngr1-/-) had significantly greater bacterial colonization in the brain, blood, spleen and lung when compared to Ifngr1-/- animals. While we found that mice lacking STAT2 signaling (Stat2-/-) did not display increased bacterial counts when compared to WT mice, mice lacking both STAT2 and the IFN-γ receptor (Stat2-/-/Ifngr1-/-) displayed significantly increased counts of Brucella within the brain and blood, and developed neurologic symptoms at an elevated rate when compared to Ifngr1-/- mice. Our findings indicate that IFN signaling through both STAT1 and STAT2 has a complex and important role in protecting against bacterial colonization and development of neurologic symptoms following infection by Brucella. Funding Sources Supported by NIH T32OD011126-44; NIH 1R21AI178158-01; NIH 1R21AI153074 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)