AUTHOR=Ricci-Azevedo Rafael , Roque-Barreira Maria-Cristina , Gay Nicholas J. 

TITLE=Targeting and Recognition of Toll-Like Receptors by Plant and Pathogen Lectins

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01820

DOI=10.3389/fimmu.2017.01820

ISSN=1664-3224

ABSTRACT=We have reported that some lectins act as agonists of TLRs and have immunomodulatory properties. The plant lectin ArtinM interacts with N-glycans of TLR2, whereas other lectins of microbial origin interact with TLR2 and TLR4. Expression of the receptors on the surface of antigen-presenting cells exposes N-glycans that may be targeted by lectins of different structures, specificities, and origins. These interactions trigger cell signaling that leads to NF-kB activation and production of the Th1 polarizing cytokine IL-12. In vivo, the administration of an active lectin to mice infected with an intracellular pathogen is followed by the same sequence of events, conferring resistance to the pathogen. The human pathogens Toxoplasma gondii (TgMIC1 and TgMIC4) and Paracoccidioides brasiliensis (Paracoccin, PCN) by recognition and activation of TLR2 and TLR4 induce cell events and in vivo effects comparable to the promoted by ArtinM. In this article, we highlight these two distinct mechanisms for activating antigen presenting cells. TLRs act as sensors for the presence of conventional pathogen-associated molecular patterns such as microbial lipids. On the other hand, our results show that there is an alternative way to trigger TLR-mediated cell activation, in which lectins bind to receptor N-glycans and stimulate activation of cells, leading to expression of pro-inflammatory cytokines. This process may lead to the development of new pharmaceutical tools that are effective promoters of protective immune responses directed against intracellular pathogens and potentially tumors.