Leukocyte Immunoglobulin-Like Receptors in Regulating the Immune Response in Infectious Diseases: A Window of Opportunity to Pathogen Persistence and a Sound Target in Therapeutics

Abstract

Immunoregulatory receptors are essential for orchestrating an immune response as well as appropriate inflammation in infectious and non-communicable diseases. Among them, leukocyte immunoglobulin-like receptors (LILRs) consist of activating and inhibitory receptors that play an important role in regulating immune responses modulating the course of disease progression. On the one hand, inhibitory LILRs constitute a safe-guard system that mitigates the inflammatory response, allowing a prompt return to immune homeostasis. On the other hand, because of their unique capacity to attenuate immune responses, pathogens use inhibitory LILRs to evade immune recognition, thus facilitating their persistence within the host. Conversely, the engagement of activating LILRs triggers immune responses and the production of inflammatory mediators to fight microbes. However, their heightened activation could lead to an exacerbated immune response and persistent inflammation with major consequences on disease outcome and autoimmune disorders. Here, we review the genetic organisation, structure and ligands of LILRs as well as their role in regulating the immune response and inflammation. We also discuss the LILR-based strategies that pathogens use to evade immune responses. A better understanding of the contribution of LILRs to host–pathogen interactions is essential to define appropriate treatments to counteract the severity and/or persistence of pathogens in acute and chronic infectious diseases lacking efficient treatments.

Expression of immune response genes in human corneal epithelial cells interacting with Aspergillus flavus conidia

“…Leukocyte immunoglobin-like receptors (LILRs) consists of 11 receptors with extracellular Ig-like domains, categorized into inhibitory (LILRB1-B5) and activating (LILRA1-A6 except A3) and reported to be expressed mostly in neutrophils [ 55 ]. LILRB2 suppress immune cell activity and mainly reported in viral, bacterial and parasite infection [ 56 ]. Recently it has been shown that LILRB2 is up-regulated in corneal tissues of bacterial keratitis.…”

Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy

“…The expanding LILRB field has begun to explore the importance of these receptors in immune dysregulation; however, little is known about their involvement in infection ( 89 ). As recently reviewed by Abdallah et al, a considerable number of pathogens are capable of interacting directly with LILRB family members to induce immunosuppression, which may prove especially pertinent during both ongoing and overt responses to infection ( 90 ). Conversely, blocking the interaction between LILRBs and pathogenic ligands may mitigate the immunoevasion that pathogens employ to prolong infection and perpetuate survival.…”

Podocalyxin Expressed in Antigen Presenting Cells Promotes Interaction With T Cells and Alters Centrosome Translocation to the Contact Site

“…The tolerogenic capability of DCs relies on their maturation state, the presence of anti-inflammatory molecules and the type of microbial stimuli ( 6 ). The induction of immunity or tolerance depends on the balance between activating and inhibitory processes ( 7 ). Therefore, the identification of molecules that elicit immunomodulatory effects may provide new therapeutic strategies to treat infectious and malignant diseases ( 7 , 8 ).…”

“…The induction of immunity or tolerance depends on the balance between activating and inhibitory processes ( 7 ). Therefore, the identification of molecules that elicit immunomodulatory effects may provide new therapeutic strategies to treat infectious and malignant diseases ( 7 , 8 ).…”