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Antigen-presenting cells (APCs) are present throughout the human body ‒ in tissues, at barrier sites and in the circulation. They are critical for processing external signals to instruct both local and systemic responses towards immune tolerance or immune defense. APCs express an extensive repertoire of pattern-recognition receptors (PRRs) to detect and transduce these signals. C-type lectin receptors (CLRs) comprise a subfamily of PRRs dedicated to sensing glycans, including those expressed by commensal and pathogenic bacteria. This review summarizes recent findings on the recognition of and responses to bacteria by membrane-expressed CLRs on different APC subsets, which are discussed according to the primary site of infection. Many CLR-bacterial interactions promote bacterial clearance, whereas other interactions are exploited by bacteria to enhance their pathogenic potential. The discrimination between protective and virulence-enhancing interactions is essential to understand which interactions to target with new prophylactic or treatment strategies. CLRs are also densely concentrated at APC dendrites that sample the environment across intact barrier sites. This suggests an -as yet- underappreciated role for CLR-mediated recognition of microbiota-produced glycans in maintaining tolerance at barrier sites. In addition to providing a concise overview of identified CLR-bacteria interactions, we discuss the main challenges and potential solutions for the identification of new CLR-bacterial interactions, including those with commensal bacteria, and for in-depth structure-function studies on CLR-bacterial glycan interactions. Finally, we highlight the necessity for more relevant tissue-specific in vitro, in vivo and ex vivo models to develop therapeutic applications in this area.

Made available in DSpace on 2018-11-26T15:44:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-23 United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC) Bovine herpesvirus-4 (BoHV-4) and bovine viral diarrhea virus (BVDV) infect the uterus of cattle, often resulting in reduced fertility, or abortion of the fetus, respectively. Here, exposure of primary bovine endometrial cells to BoHV-4 or BVDV modulated the production of inflammatory mediators. Viral pathogen-associated molecular patterns (PAMPs) are detected via pattern-recognition receptors (PRRs). However, the relative contribution of specific PRRs to innate immunity, during viral infection of the uterus, is unclear. Endometrial epithelial and stromal cells constitutively express the PRR Toll-like receptor (TLR)-3, but, the status of retinoic acid-inducible gene I (RIG-I), a sensor of cytosolic nucleic acids, is unknown. Primary endometrial epithelial and stromal cells had low expression of RIG-I, which was increased in stromal cells after 12 h transfection with the TLR3 ligand Poly(I:C), a synthetic analog of double-stranded RNA. Furthermore, short interfering RNA targeting TLR3, or interferon (IFN) regulatory transcription factor 3, an inducer of type I IFN transcription, reduced Poly(I:C)-induced RIG-I protein expression and reduced inflammatory mediator secretion from stromal cells. We conclude that antiviral defense of endometrial stromal cells requires coordinated recognition of PAMPs, initially via TLR3 and later via inducible RIG-I. Swansea Univ, Med Sch, Inst Life Sci, Swansea, W Glam, Wales Univ Estadual Paulista, Fac Agr & Vet Sci, Jaboticabal, Brazil Univ Parma, Dept Med Vet Sci, Parma, Italy Univ Estadual Paulista, Fac Agr & Vet Sci, Jaboticabal, Brazil United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC): BB/1017240/1

Plants are constantly exposed to potentially pathogenic microbes present in their surrounding environment. Due to the activation of the pattern-triggered immunity (PTI) response that largely relies on accurate detection of pathogen- or microbe-associated molecular patterns by pattern-recognition receptors (PRRs), plants are resistant to the majority of potential pathogens. However, adapted pathogens may avoid recognition or repress plant PTI and resulting diseases significantly affect crop yield worldwide. PTI provides protection against a wide range of pathogens. Reinforcement of PTI through genetic engineering may thus generate crops with broad-spectrum field resistance. In this review, new approaches based on fundamental discoveries in PTI to improve crop immunity are discussed. Notably, we highlight recent studies describing the interfamily transfer of PRRs or key regulators of PTI signalling.