Abstract
BackgroundThe high mobility group box 1 (HMGB1) is the prototype of alarmin protein released by stressed or dying cells. The redox state of this protein confers different functions in the regulation of inflammation and immune response.AimDetermine the kinetics, cellular sources and function of HMGB1 in experimental tuberculosis.MethodsBALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv. At different time points, HMGB1 was quantified in bronchial lavage fluid (BALF) and in lungs was determined its cellular sources by immunohistochemistry. HMGB1 was blocked with specific antibodies or 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 epithelium and macrophages were the most important sources. At day 7 to 21 the oxidized HMGB1 was predominant, while during late infection only the reduced form was seen. Blocking HMGB1 during early infection produced significant decrease of bacilli burdens and high production of pro-inflammatory cytokines, while the opposite was seen when HMGB1 was administered. Blocking HMGB1 activity or administrated it in high amounts during late infection worsening the disease.ConclusionsHMGB1 is liberated during experimental tuberculosis and promotes or suppress the immune response and inflammation depending on the redox state.
Highlights
Tuberculosis (TB) is a respiratory chronic infection which produces profound abnormalities in the immune system [1]
high mobility group box 1 (HMGB1) is liberated during experimental tuberculosis and promotes or suppress the immune response and inflammation depending on the redox state
Innate immunity senses the presence of the pathogen after the participation of a number of pattern-recognition receptors that detect mycobacterial components though pathogen-associated molecular patterns (PAMPs), being the Toll-like receptors (TLRs) the best studied of these pattern detectors
Summary
Tuberculosis (TB) is a respiratory chronic infection which produces profound abnormalities in the immune system [1]. Both innate and acquired immunity are essential participants in the growth control of Mycobacterium tuberculosis (Mtb). Besides to recognizing PAMPs, the immune system has evolved to detect endogenous danger signals or by analogy damage-associated molecular patterns (DAMPs), which are released by dying cells or are actively secreted by stressed cells and contributes to regulate the inflammatory response [2]. The nuclear DNA-binding molecule high mobility group box 1 (HMGB1) is a prototype DAMP protein that may play a role in modulating the inflammatory responses after the cell damage induced by Mtb [3]. The redox state of this protein confers different functions in the regulation of inflammation and immune response
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