The Role of IL-36 in Infectious Diseases: Potential Target for COVID-19?

Abstract

IL-36 is a member of the interleukin 1 cytokine family, which is currently experiencing a renaissance due to the growing understanding of its context-dependent roles and advances in our understanding of the inflammatory response. The immunological role of IL-36 has revealed its profound and indispensable functional roles in psoriasis, as well as in several inflammatory diseases, including inflammatory bowel disease (IBD), systemic lupus erythematosus, rheumatoid arthritis (RA) and cancer. More recently, an increasing body of evidence suggests that IL-36 plays a crucial role in viral, bacterial and fungal infections. There is a growing interest as to whether IL-36 contributes to host protective immune responses against infection as well as the potential implications of IL-36 for the development of new therapeutic strategies. In this review, we summarize the recent progress in understanding cellular expression, regulatory mechanisms and biological roles of IL-36 in infectious diseases, which suggest more specific strategies to maneuver IL-36 as a diagnostic or therapeutic target, especially in COVID-19.

Differential anti-viral response to respiratory syncytial virus A in preterm and term infants

“…Mouse studies of exogenous IL-36γ delivery have shown that it improves bacterial and viral clearance and leads to reduced morbidity and mortality by improving pro-inflammatory and anti-viral responses. 63 Validating our findings of increased term infant IL-36γ and IL-10 in a clinical cohort would be critical to understanding disease susceptibility in preterm infants. This can be achieved by combining paediatric peripheral blood samples with mucosal samples from RSV infected infants to provide a more complete snapshot of the immune response to RSV and then comparing these factors between those with severe and moderate disease.…”

Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation

“…IL36 is notable as a member of the IL1 superfamily of pro-inflammatory cytokines, which help regulate the adaptive and innate immune systems. 74 IL36 promotes antiviral immunity by increasing cellular sensitivity to interferon 75 in human and mouse models to herpes simplex virus 75 and a host of other viruses. 74

Figure 6 Evidence for a potential link between immunity and the recombination landscape in Myotis bats Distribution of phylogenomic signal, recombination rate, ibl, and f( D ) values for chromosome V15 for the bechsteinii clade.

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“… 74 IL36 promotes antiviral immunity by increasing cellular sensitivity to interferon 75 in human and mouse models to herpes simplex virus 75 and a host of other viruses. 74

Figure 6 Evidence for a potential link between immunity and the recombination landscape in Myotis bats Distribution of phylogenomic signal, recombination rate, ibl, and f( D ) values for chromosome V15 for the bechsteinii clade. A large introgressed block for myotis and daubentonii ( Figure S24 ) is highlighted in red and is significantly enriched for IL-36 and IL-1 signaling pathways (FDR < 0.05) ( Table S8 ).

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The Interplay between Candida albicans, Vaginal Mucosa, Host Immunity and Resident Microbiota in Health and Disease: An Overview and Future Perspectives

“…The former is induced by the interaction of the C. albicans proteins Ssa1p and Als3p with cadherins and EGFR/Her2 [ 25 , 26 , 28 , 29 ], while the latter occurs when the growing hyphal tip pushes the epithelial cell membrane and leads to cell damage through the release of various virulence factors, including the cytolytic peptide toxin candidalysin, secretory aspartyl proteinases (SAPs), lipases and phospholipases. Recognition of the filamentous forms of Candida by VECs leads to sustained activation of all three mitogen-activated protein kinase (MAPK) pathways (p38, JNK and ERK1/2), which in turn, leads to c-fos activation via p38 and release of antimicrobial peptides, such as alarmins and pro-inflammatory cytokines (GM-CSF, G-CSF, IL-6, IL-1α, IL-1β, IL-36γ and CCL20) that are essential for the recruitment of innate immune cells, mainly neutrophils and macrophages [ 18 , 20 , 30 , 31 , 32 , 33 , 34 ]. Several recent investigations showed that fungal components, i.e., candidalysin [ 35 , 36 , 37 ] and SAPs, as well as the intracellular damage-responsive molecular complex, called the NLRP3 inflammasome, of VECs [ 38 , 39 , 40 , 41 ] are all critical actors in VVC immunopathology.…”