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

Abstract

The activating leukocyte immunoglobulin-like receptors (LILRAs) play an important role in innate immunity. However, most of the LILRA members have not been characterized in avian species including chickens. The present study is the first attempt at cloning, structural analysis and functional characterization of two LILRAs (LILRA2 and LILRA6) in chickens. Multiple sequence alignments and construction of a phylogenetic tree of chicken LILRA2 and LILRA6 with mammalian proteins revealed high conservation between chicken LILRA2 and LILRA6 and a close relationship between the chicken and mammalian proteins. The mRNA expression of LILRA2 and LILRA6 was high in chicken HD11 macrophages and the small intestine compared to that in several other tissues and cells tested. To examine the function of LILRA2 and LILRA6 in chicken immunity, LILRA2 and LILRA6 were transfected into HD11 cells. Our findings indicated that LILRA2 and LILRA6 are associated with the phosphorylation of Src kinases and SHP2, which play a regulatory role in immune functions. Moreover, LILRA6 associated with and activated MHC class I, β2-microglobulin and induced the expression of transporters associated with antigen processing but LILRA2 did not. Furthermore, both LILRA2 and LILRA6 activated JAK-STAT, NF-κB, PI3K/AKT and ERK1/2 MAPK signaling pathways and induced Th1-, Th2- and Th17-type cytokines and Toll-like receptors. Collectively, this study indicates that LILRA2 and LILRA6 are essential for macrophage-mediated immune responses and they have the potential to complement the innate and adaptive immune system against pathogens.

Leukocyte Immunoglobulin-like Receptor A5 Deletion Aggravates the Pathogenesis of Pseudomonas aeruginosa Keratitis by Promoting Proinflammatory Cytokines

“…27,28 LILRs also serve immunomodulatory roles in bacterial infection. [16][17][18][19][29][30][31][32][33] Unknown is the function of LILRA5 in bacterial infection. We found that LILRA5 deletion negatively regulates the immune responses in P. aeruginosa keratitis by promoting the expression of proinflammatory cytokines and TLR4 in neutrophils.…”

LncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch-Schonlein purpura rats

“…Moreover, the expression of miRNA-181a-5p is downregulated in the monocytes of obese subjects and cardiovascular disease patients [ 30 ]. SHP2 plays a vital role in regulating macrophage proliferation via a direct activation of the MAPK pathway [ 31 ]. A previous study has shown that the inactivation of SHP2 can augment IL-4-mediated enhancement of M2 polarization in vitro [ 32 ].…”

IncRNA MEG8 sponging miR-181a-5p contributes to M1 macrophage polarization by regulating SHP2 expression in Henoch Schonlein purpura rats

“…Abnormal expression of lncRNAs is involved in the pathogenesis of various diseases [24]. Recent studies have suggested that lncRNAs potentially impact the expression levels of miRNA targets by competing for miRNAs [25]. Evidences have shown that MEG8 contributed to epigenetic progression of EMT of lung and pancreatic cancer cells, and suppressed the proliferation and migration of both the vascular smooth muscle cell (VSMC) and trophoblast cells [26,27].…”