Abstract
Background:
High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases.
Principal findings:
We have previously identified a High mobility group B protein from Trypanosoma cruzi (TcHMGB) and showed that it has architectural properties interacting with DNA like HMGBs from other eukaryotes. Here we show that TcHMGB can be translocated to the cytoplasm and secreted out of the parasite, a process that seems to be stimulated by acetylation. We report that recombinant TcHMGB is able to induce an inflammatory response in vitro and in vivo, evidenced by the production of Nitric Oxide and induction of inflammatory cytokines like TNF-α, IL-1β and IFN-γ gene expression. Also, TGF-β and IL-10, which are not inflammatory cytokines but do play key roles in Chagas disease, were induced by rTcHMGB.
Conclusions:
These preliminary results suggest that TcHMGB can act as an exogenous immune mediator that may be important for both the control of parasite replication as the pathogenesis of Chagas disease and can be envisioned as a pathogen associated molecular pattern (PAMP) partially overlapping in function with the host DAMPs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Nucleus / metabolism
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Chagas Disease / genetics
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Chagas Disease / immunology*
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Chagas Disease / parasitology
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HMGB Proteins / genetics
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HMGB Proteins / immunology*
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HMGB Proteins / metabolism
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Humans
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Inflammation Mediators / immunology*
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Nitric Oxide / immunology
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Protein Transport
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Protozoan Proteins / metabolism
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Trypanosoma cruzi / genetics
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Trypanosoma cruzi / immunology*
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Trypanosoma cruzi / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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HMGB Proteins
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Inflammation Mediators
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Protozoan Proteins
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Nitric Oxide
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Interferon-gamma
Grants and funding
This work was funded by the Bilateral International Project Argentina-Mexico number 190527, Consejo Nacional de Investigaciones Científicas y Técnicas Argentina-Consejo Nacional de Ciencia y Tecnología Mexico,
http://www.conicet.gov.ar/,
http://www.conacyt.mx/ to PC and RHP, Subsidios para Investigación de la Enfermedad de Chagas 2012, Fundación Bunge y Born.
http://www.fundacionbyb.org/ to PC; and PIP 2011-01-00372, Consejo Nacional de Investigaciones Científicas y Técnicas
http://www.conicet.gov.ar/ to PC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.