The role of lectins in allergic sensitization and allergic disease Fabián Salazar, MSc, Herb F. Sewell, MBChB, PhD, FRCP, FRCPath, Farouk Shakib, PhD, FRCPath, Amir M. Ghaemmaghami, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 132, Issue 1, Pages 27-36 (July 2013) DOI: 10.1016/j.jaci.2013.02.001 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 The domain structure of lectins: schematic representation of the polypeptide and domain structures of membrane-associated CLRs (A),5-8 soluble lectins (B),9 and galectins (C).10 CRD, Carbohydrate recognition domain; COR, collagen region; CysD, cysteine-rich domain; FNII, fibronectin type II–like domain; iITAM, incomplete immunoreceptor tyrosine-based activation motif; NLR, nonlectin region; TM, transmembrane region. Journal of Allergy and Clinical Immunology 2013 132, 27-36DOI: (10.1016/j.jaci.2013.02.001) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Interaction between CLRs and TLRs. A, Antagonistic effect between the MR and DC-SIGN. Both the MR and DC-SIGN have been shown to recognize and internalize Der p 1 but with opposite consequences.14,18 Moreover, Der p 1 has been shown to downregulate the expression of DC-SIGN,30 and it can also cleave DC-SIGN.29 B, Interaction between the MR and TLRs. Binding of Man-LAMs to the MR inhibits the production of IL-12 after exposure to LPS.36,38 Der p 2 binds to the MR on DCs, leading to a TH2 response, as well as activating TLR4 signaling.14,32 OVA mediates the upregulation of both the MR and TLR2 and is able to bind to the MR and possibly trigger these effects.33 There is production of IL-8 after exposure to P carinii in a cell line that coexpresses the MR and TLR2.31 C, Interaction between DC-SIGN and TLR4. The ligation of DC-SIGN with Man-LAMs inhibits the production of IL-12 after exposure to LPS but increases the production of IL-10.34,39 Both DC-SIGN and TLR4 are involved in the response to Schistosoma mansoni glycolipids.37 D, Interaction between Dectin-1 and TLR2. In macrophages the ligation of Dectin-1 alone with zymosan leads to the secretion of reactive oxygen species (ROS), and simultaneous ligation of Dectin-1 and TLR2 enhances the secretion of IL-12 and TNF-α at levels higher than those induced by TLR2 alone.35 Activating signals are shown in green, and inhibitory signals are shown in red. Journal of Allergy and Clinical Immunology 2013 132, 27-36DOI: (10.1016/j.jaci.2013.02.001) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 The role of lectins in allergy: synergistic and antagonistic effects of lectins in allergy. The MR is able to recognize and internalize Der p 1, leading to a TH2 response.14 DC-SIGN can also bind and internalize Der p 1, but that engagement leads to a TH1 response.18 Moreover, Der p 1 can cleave DC-SIGN and downregulates its expression on DCs as well.29,30 Dectin-2 can recognize different extracts from HDMs and triggers cysteinyl leukotriene (cys-LT).19 Furthermore, Dectin-2 is crucial in eosinophilic (E) and neutrophilic (N) pulmonary inflammation and TH2 cytokine production.41 Both SP-A and SP-D have been shown to bind HDM extracts and in that way block the proliferation of PBMCs.9 Moreover, they reduce the proliferation of B cells (BC) and shift the response to a TH1 profile.9 On the other hand, Der p 1 can degrade and inactivate both SP-A and SP-D, favoring an allergic response.44 Finally, Gal-3 has been shown to enhance epithelial cell–lymphocyte (EC-L) interactions, possibly through its glycans.63 On the other hand, Gal-9 is able to bind IgE and in that way blocks the asthmatic reaction.64 Red arrows represent proallergic responses, and green arrows represent antiallergic responses. Journal of Allergy and Clinical Immunology 2013 132, 27-36DOI: (10.1016/j.jaci.2013.02.001) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Some immune and nonimmune processes in which lectins are involved. Lectins participate in different immune and nonimmune processes, such as cell trafficking, cellular signaling, pathogen recognition, antigen presentation, immune tolerance, cancer progression, and allergen recognition. Journal of Allergy and Clinical Immunology 2013 132, 27-36DOI: (10.1016/j.jaci.2013.02.001) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions