http://precedings.nature.com/tags/innate%20immune%20response Recently posted documents tagged with 'innate immune response' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/2005/version/1 Current thinking emphasizes the primacy of CD14 in facilitating TLR recognition of microbes to initiate proinflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of Borrelia burgdorferi not only triggers an inflammatory response in the absence of CD14, but one that is uncontrolled as a consequence of impaired PI3K/AKT/p38-MAPK signaling and negative regulation of TLR2. CD14 deficiency results in hyperphosphorylation of AKT and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS thereby engendering a more severe and persistent inflammatory response to B. burgdorferi. Perturbation of this CD14/p38-MAPK-dependent mechanism of immune regulation may underlie development of infectious chronic inflammatory syndromes. http://precedings.nature.com/documents/2005/version/1 Wed, 25 Jun 2008 10:07:23 UTC CD14 Modulates PI3K/AKT/p38-MAPK Licensing of Negative Regulators of TLR Signaling to Restrain Chronic Inflammation hdl:10101/npre.2008.2005.1 2008-07-01 Timothy J. Sellati Nature Precedings 2008-06-25T10:07:23Z Manuscript Immunology Microbiology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/930/version/1 Trichophyton rubrum is the main agent causing dermatophytosis (1). Keratinocytes areconsidered to be the first physical barrier of defense against pathogens (2). But notonly a physical barrier. They recognize antigens through Toll like receptors (TLR) (3).The activation of this TLR, present on the surface of the keratinocytes, induce theexpression of different pro-inflammatory cytokines, co-stimulatory molecules andantimicrobial peptides such as β-defensins (4).The main objective of this work is to determine if lipopolysaccharides of G – bacteria(LPS), lipotheichoic acid from G+ bacteria (LTA), and conidias, isolated from T. rubrumwere able to activate the expression of TLR2 and TLR6 on the cell surface of a primaryculture of human keratinocytes through Flow cytometry. Furthermore we are looking forthe presence of β-defensins 1 and 2, IL-1b and IL-8 in the supernatant, of the abovementioned culture of cells, by Western blot.From the flow cytometry data, the preliminary results showed an important dispersionin terms of proliferation, increase in size and granularity of keratinocytes, from primarycultures of skin from healthy donors, stimulated 6 hours with conidias of T. rubrum, andLTA, but not when non stimulated, or stimulated with LPS (Fig 1).When keratinocytes from primary cultures of skin from healthy donors were cultivated48 hours, it was found dispersion in terms of proliferation, increase in size andgranularity when stimulated with conidias of T. rubrum, and LPS but not when nonstimulated, or stimulated with LTA (Fig 2).The keratinocytes expressed increased levels of TLR2 and TLR6 when werestimulated with LTA and less to T. rubrum, in the 6 hours cultures, but this last cells stillshowed increased size (Fig 3).The Keratinocytes expressed increased levels of TLR2 in the 48 hours cultures whenwere stimulated with LPS and T. rubrum.(Fig 4)Besides, β-defensin-2 was detected in the supernatant of cultures of keratinocytesstimulated with LPS (Fig 5).It can preliminary be concluded that keratinocytes from primary cultures of human skin from healthy donors, are cells that respond as typical immune cells, after stimulationwith T. rubrum, LTA and LPS in different conditions, and that this mechanism may bevery important, for the protection of local environment. References1.- Arenas R., Dermatofitosis en México. Rev Iberoam Micol 2002; 19: 63-67.2.- Kupper T. and Fuhlbrigge R. Immune surveillance in the skin: mechanims and clinical consecuences.Nat Rev Immunol 2004; 4: 211-2223.- Kôllish G., Naderi B., Voelcker V., Wallich R., Behrendt H., Ring J., Bauer S., Jacob T., Mempel M. andOlelrt M. Various members of the Toll-Like receptor family contribute to the innate immune response ofhuman epidermal keratinocytes. Immunology 2005; 114: 531-541.4.- Akira, S. and Takeda K. 2004. Toll-like Receptor Signalling. Nature Reviews Immunology 4:499-511. http://precedings.nature.com/documents/930/version/1 Thu, 06 Sep 2007 15:21:03 UTC Keratinocytes from human skin respond as typical immune cells after the stimulation with Trichophyton rubrum hdl:10101/npre.2007.930.1 2007-09-06 Alfonso E. Islas-Rodríguez Nature Precedings 2007-09-06T15:21:03Z Manuscript Immunology Microbiology Molecular Cell Biology http://creativecommons.org/licenses/by/2.5/