Toll-Like Receptor 2 Mediates In Vivo Pro- and Anti-inflammatory Effects of Mycobacterium Tuberculosis and Modulates Autoimmune Encephalomyelitis.


:Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3(+) Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.


Front Immunol


Frontiers in immunology


Piermattei A,Migliara G,Di Sante G,Foti M,Hayrabedyan SB,Papagna A,Geloso MC,Corbi M,Valentini M,Sgambato A,Delogu G,Constantin G,Ria F




Has Abstract


2016-05-24 00:00:00








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    abstract::Mechanisms driving acute graft-versus-host disease (aGVHD) onset in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still poorly understood. To provide a detailed characterization of tissue-infiltrating T lymphocytes (TL) and search for eventual site-specific specificities, we de...

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    authors: Alhaj Hussen K,Michonneau D,Biajoux V,Keita S,Dubouchet L,Nelson E,Setterblad N,Le Buanec H,Bouaziz JD,Guimiot F,Socié G,Canque B

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  • Structural Basis of IL-1 Family Cytokine Signaling.

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    authors: Shinko D,McGuire HM,Diakos CI,Pavlakis N,Clarke SJ,Byrne SN,Charles KA

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    authors: Duquesnoy RJ

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    pub_type: 杂志文章,评审


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    更新日期:2016-06-24 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Panda D,Gjinaj E,Bachu M,Squire E,Novatt H,Ozato K,Rabin RL

    更新日期:2019-05-15 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Hussain K,Letley DP,Greenaway AB,Kenefeck R,Winter JA,Tomlinson W,Rhead J,Staples E,Kaneko K,Atherton JC,Robinson K

    更新日期:2016-03-07 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Fabersani E,Abeijon-Mukdsi MC,Ross R,Medina R,González S,Gauffin-Cano P

    更新日期:2017-03-13 00:00:00

  • Role of Epstein-Barr Virus in Pathogenesis and Racial Distribution of IgA Nephropathy.

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Zachova K,Kosztyu P,Zadrazil J,Matousovic K,Vondrak K,Hubacek P,Julian BA,Moldoveanu Z,Novak Z,Kostovcikova K,Raska M,Mestecky J

    更新日期:2020-02-28 00:00:00