Identification of an Activating Chicken Ig-like Receptor Recognizing Avian Influenza Viruses

Abstract

Chicken Ig-like receptors (CHIRs) represent a multigene family encoded by the leukocyte receptor complex that encodes a variety of receptors that are subdivided into activating CHIR-A, inhibitory CHIR-B, and bifunctional CHIR-AB. Apart from CHIR-AB, which functions as an Fc receptor, CHIR ligands are unknown. In the current study, we used a panel of different BWZ.36 CHIR reporter cells to identify an interaction between specific CHIRs and avian influenza virus (AIV). The specificity of the CHIR-AIV interaction was further demonstrated using CHIR fusion proteins that bound to AIV-coated plates and were able to reduce the interaction of reporter cells with AIV. There was no difference in binding of CHIR to different AIV strains. Furthermore, CHIR fusion proteins reduced AIV-induced in vitro activation of NK cells obtained from lungs of AIV-infected animals, as judged by the lower frequency of CD107 cells. Because the original CHIR reporter lines were generated based on sequence information about extracellular CHIR domains, we next identified a full-length CHIR that displayed similar binding to AIV. The sequence analysis identified this CHIR as a CHIR-A. Neuraminidase treatment of coated CHIR-human Ig proteins reduced binding of trimeric H5 proteins to CHIR. This suggests that the interaction is dependent on sialic acid moieties on the receptor. In conclusion, this article identifies AIV as a ligand of CHIR-A and describes the functional consequences of this interaction.

Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian Macrophages and Modulate Cytokine Production by Activating Multiple Signaling Pathways

“…The LILRA genes, including LILRA1–6 , play an important role in the immune system of humans [ 1 , 7 ]. In chicken, some genes of the Ig superfamily such as TREM, CD300, SIRP, chicken Ig-like receptors (CHIR)-A, CHIR-B, CHIR-AB homologs and chicken leukocyte immunoglobulin receptor (LIR) were identified using bioinformatics approaches that may be important role in immune responses to high and low avian influenza virus [ 4 , 19 , 20 , 21 ]. However, functional characterization of the activating group of these genes has not yet been carried out in avian species including chickens.…”

“…The leukocyte immunoglobulin-like receptor (LILR) family consists of members that play inhibitory or activating roles on the genes of the proteins involved with the immune system and expressed in several primary innate immune cells (monocyte/macrophages, dendritic cells and CD4 + /CD8 + T cells) [ 1 , 2 , 3 ] and cell lines (HEK293 T cells, MDCK cells, HL-60 cells, thymoma BWZ.36 cells, epithelial cells and T cells) [ 1 , 4 , 5 , 6 ]. The LILR genes are highly homologous in the sequence of the extracellular regions and different in their sequences of the intracellular regions [ 7 , 8 ].…”

“…Recent studied demonstrated that chicken leukocyte immunoglobulin receptor (LIR) are shown highly homologous with chicken Ig-like receptors (CHIR) family genes and also play an important role to recognize avian influenza [ 4 ]. On the other hand, some members of the Ig superfamily in chicken were identified and characterized of functions that may be involved in immune responses such as triggering receptor expressed on myeloid cells (TREM), cluster of differentiation (CD) 300, signal-regulatory protein alpha (SIRP), CHIR-A, CHIR-B and CHIR-AB homologs [ 4 , 19 , 20 , 21 ]. Moreover, there is no information on the primary structure and function of LILRA2 and LILRA6 in avian species.…”

Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of major histocompatibility complex class I genes and signaling pathways

“…Moreover, the gene expression and polymorphisms of LILRBs have been reported to be associated with autoimmune and infectious diseases such as those caused by Salmonella [8], cytomegalovirus [9], and Mycobacterium tuberculosis [10], as well as rheumatoid arthritis [11], Alzheimer’s model [12], psoriatic arthritis [13], HIV/AIDS [14], and cancer [6]. Recently, some members of the Ig superfamily that may be involved in immune responses such as triggering receptor expressed on myeloid cells, cluster of differentiation 300, signal regulatory protein and chicken Ig-like receptors (CHIR)-A, CHIR-B, and CHIR-AB homologs were identified in chicken using bioinformatics approaches [15]. The studies of the chicken leukocyte immunoglobulin receptor (LIR) indicated that LIR genes are shown highly polymorphic locus harboring a variable number of CHIR genes and also play an important role in avian influenza infection in chicken [15].…”

Intestinal microbiota and broiler health: hype or hope?

“…Systemically, microbiota can induce instructive signals to non-mucosal antigen-presenting cells and by producing among others IL-15, TNFα and IFN, subsequently prime optimal splenic NK cell responses (Ganal et al, 2012). Since chicken NK cells have been shown to express TLRs (Kannaki et al, 2010) and NCRs (Straub et al, 2013, Jansen et al, 2016, the interactions between microbiota and NK cells probably follow similar routes to those in humans and mice.…”