The contribution of Toll-like receptor 2 to the innate recognition of a Leishmania infantum silent information regulator 2 protein

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Ricardo Silvestre (Author) Other; Ana M Silva (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Ali Ouaissi (Author) Other

Journal

Title: Immunology

Vol. 128 No. 4

Pages: 484-499

ISSN: 0019-2805

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 15 Citations

ISI Web of Science

Scopus - 18 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences

Other information

Authenticus ID: P-003-DYJ

DOI: 10.1111/j.1365-2567.2009.03132.x

Resumo (PT): We have characterized a Leishmania protein belonging to the silent information regulator 2 (SIR2) family [SIR2 related protein 1 (SIR2RP1)] that might play an immunoregulatory role during infection through its capacity to trigger B-cell effector functions. We report here that SIR2RP1 leads to the proliferation of activated B cells, causing increased expression of major histocompatibility complex (MHC) II and the costimulatory molecules CD40 and CD86, which are critical ligands for T-cell cross-talk during the development of adaptive immune responses. In contrast, B cells isolated from Toll-like receptor 2 (TLR2) knockout mice were unable to respond to the SIR2RP1 stimulus. Similarly, SIR2RP1 induced the maturation of dendritic cells (DCs) in a TLR2-dependent manner with the secretion of pro-inflammatory cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)-α] and enhanced the costimulatory properties of DCs. Nevertheless, immunization assays demonstrated that TLR2-deficient mice were able to mount a specific humoral response to SIR2RP1. Interestingly, further investigations showed that macrophages were activated by SIR2RP1 even in the absence of TLR2. Therefore, a different type of interplay between SIR2RP1 and the major antigen-presenting cells in vivo could explain the immune response observed in TLR2-deficient mice. Together, these results demonstrate that TLR2 signalling contributes to SIR2RP1 recognition by innate immune host cells <br> <br> <a target="_blank" href="http://web.ebscohost.com/ehost/detail?hid=104&sid=9228c87e-ed25-4f3a-95bf-0a1d69c0c398%40sessionmgr115&vid=3&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=a9h&AN=45037623"> Texto integral </a> <br> <br>

Abstract (EN): P>We have characterized a Leishmania protein belonging to the silent information regulator 2 (SIR2) family [SIR2 related protein 1 (SIR2RP1)] that might play an immunoregulatory role during infection through its capacity to trigger B-cell effector functions. We report here that SIR2RP1 leads to the proliferation of activated B cells, causing increased expression of major histocompatibility complex (MHC) II and the costimulatory molecules CD40 and CD86, which are critical ligands for T-cell cross-talk during the development of adaptive immune responses. In contrast, B cells isolated from Toll-like receptor 2 (TLR2) knockout mice were unable to respond to the SIR2RP1 stimulus. Similarly, SIR2RP1 induced the maturation of dendritic cells (DCs) in a TLR2-dependent manner with the secretion of pro-inflammatory cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)-alpha] and enhanced the costimulatory properties of DCs. Nevertheless, immunization assays demonstrated that TLR2-deficient mice were able to mount a specific humoral response to SIR2RP1. Interestingly, further investigations showed that macrophages were activated by SIR2RP1 even in the absence of TLR2. Therefore, a different type of interplay between SIR2RP1 and the major antigen-presenting cells in vivo could explain the immune response observed in TLR2-deficient mice. Together, these results demonstrate that TLR2 signalling contributes to SIR2RP1 recognition by innate immune host cells.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16