Despite extensive investigation focused on both the molecular characteristics and the expression level of Toll-like receptors (TLRs) during the inflammatory response in vertebrates, few data are available in the literature on the role of these proteins in invertebrate’s immune response. Here, we propose the medicinal leech as a valuable model to better elucidate the role of TLR4 and its related products, such as tumor necrosis factor (TNF-α), after activation of the leech peripheral immune system with the endogenous medicinal leech recombinant allograft inflammatory factor-1 (rHmAIF-1) or with an exogenous stimulus, such as lipopolysaccharide (LPS). Our results indicate that activated macrophages (HmAIF-1 + ) and granulocytes (CD11b + ) express both TLR4 and its coreceptor CD14. Moreover, functional studies performed by injecting a cyanobacterium selective TLR4 antagonist CyP demonstrated that only the TLR4 pathway was blocked, while the immune response caused by lipoteichoic acid (LTA) treatment is not affected. These results are consistent with literature on vertebrates, indicating that TLR4 functions as a LPS receptor while the recognition of LTA may involve other pathways.

The medicinal leech as a valuable model for better understanding the role of a TLR4-like receptor in the inflammatory process

Girardello, Rossana
Methodology
;
Baranzini, Nicolò
Methodology
;
Molteni, Monica
Methodology
;
Rossetti, Carlo
Conceptualization
;
Tettamanti, Gianluca
Membro del Collaboration Group
;
de Eguileor, Magda
Membro del Collaboration Group
;
Grimaldi, Annalisa
Writing – Review & Editing
2019

Abstract

Despite extensive investigation focused on both the molecular characteristics and the expression level of Toll-like receptors (TLRs) during the inflammatory response in vertebrates, few data are available in the literature on the role of these proteins in invertebrate’s immune response. Here, we propose the medicinal leech as a valuable model to better elucidate the role of TLR4 and its related products, such as tumor necrosis factor (TNF-α), after activation of the leech peripheral immune system with the endogenous medicinal leech recombinant allograft inflammatory factor-1 (rHmAIF-1) or with an exogenous stimulus, such as lipopolysaccharide (LPS). Our results indicate that activated macrophages (HmAIF-1 + ) and granulocytes (CD11b + ) express both TLR4 and its coreceptor CD14. Moreover, functional studies performed by injecting a cyanobacterium selective TLR4 antagonist CyP demonstrated that only the TLR4 pathway was blocked, while the immune response caused by lipoteichoic acid (LTA) treatment is not affected. These results are consistent with literature on vertebrates, indicating that TLR4 functions as a LPS receptor while the recognition of LTA may involve other pathways.
link.springer.de/link/service/journals/00441/index.htm
Cyanobacterial product; Granulocyte; LPS; Macrophage; TLR4;
Girardello, Rossana; Baranzini, Nicolò; Molteni, Monica; Rossetti, Carlo; Tettamanti, Gianluca; de Eguileor, Magda; Grimaldi, Annalisa
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2078817
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