The Role of High Mobility Group Box 1 in the Inmunopathology of the Experimental Pulmonary Tuberculosis

ROGELIO HERNANDEZ-PANDO; JORGE BARRIOS PAYÁN; DULCE MATA ESPINOSA; BRENDA MARQUINA CASTILLO; DIEGO HERNÁNDEZ RAMIREZ; OSCAR BOTTASSO; ESTELA ISABEL BINI

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 vol. 10 p. 1 - 14

1932-6203

AbstractBackgroundThe high mobility group box 1 (HMGB1) is the prototype of alarmin protein released bystressed or dying cells. The redox state of this protein confers different functions in the regulationof inflammation and immune response.AimDetermine the kinetics, cellular sources and function of HMGB1 in experimentaltuberculosis.MethodsBALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv. At different timepoints, HMGB1 was quantified in bronchial lavage fluid (BALF) and in lungs was determinedits cellular sources by immunohistochemistry. HMGB1 was blocked with specific antibodiesor recombinant HMGB1 was administered during early or late infection. Bacilli burdens,inflammation and cytokines expression were determined.ResultsThe maximal concentration of HMGB1 in BALF was at day one of infection. Bronchial epitheliumand macrophages were the most important sources. At day 7 to 21 the oxidizedHMGB1 was predominant, while during late infection only the reduced form was seen.Blocking HMGB1 during early infection produced significant decrease of bacilli burdens andhigh production of pro-inflammatory cytokines, while the opposite was seen when HMGB1was administered. Blocking HMGB1 activity or administrated it in high amounts during lateinfection worsening the disease.ConclusionsHMGB1 is liberated during experimental tuberculosis and promotes or suppress theimmune response and inflammation depending on the redox state.