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Objective: Eosinophils are one of the least abundant leukocytes in blood circulation; however, they compensate for this sparsity by highly potent content of their granules. Their involvement in numerous pathological conditions including acute and chronic infections make them an interesting research area for the field of immunology. Eosinophils play critical roles in the maintenance of immune homeostasis through their effector and modulatory functions in shaping innate and adaptive responses. Although they are mainly known for their roles in parasitic infections, it has become increasingly clear that eosinophils function not only in fungal, bacterial and viral infections, but also in tissue repair and signaling pathways regulating mast cells, Th2 and B cells. Of all the mediators of innate immunity, pattern recognition receptors (PRRs) are of great importance in the context of the stimuli. Therefore, we analyzed and cross-checked mRNA expression profiles of membrane-bound and cytosolic PRRs by comparing EoL-1 and HL-60 human eosinophil like cell lines to human primary eosinophils in silico. Materials and Methods: Utilizing publicly available databases, we analyzed PRR repertoires of eosinophils to determine the most ideal cell line models for in vitro mechanistic studies, requiring high protein and mRNA yields. Results: Our findings revealed that toll-like receptors 2 and NOD-like receptor 3 (NLRP3) had higher basal expressions in both cell lines than human primary eosinophils as opposed to NLRP12, laboratory of genetics and physiology 2 (LGP2), Dectin-1, whose expressions were higher in primary eosinophils than in both cell lines. Conclusion: These data might attribute new physiological functions to these receptors of NLR, RIG-I like receptor and C-type lectin receptor families in eosinophil immunity. [ABSTRACT FROM AUTHOR]

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2021. The Korean Association of Immunologists.)