Recent Advancements in Computational Approaches for Tailoring Toll- like Receptors and Antimicrobial Peptides Against Candida Infections

Celal Bayar University Journal of Science, cilt.21, sa.3, ss.1-9, 2025 (Hakemli Dergi)

Despite the considerable pathogenic impact of Candida albicans in human health, the gap in understanding

the cellular recognition mechanisms and subsequent host defence activation remain insufficiently

understood. Recent insights underscore the pivotal role of Toll-like receptors (TLRs) in organising innate

immune responses against pathogens. Notably, empirical investigations over recent years have underscored

TLRs as paramount pattern-recognition receptors in mammals. TLR2, for examples, exhibits affinity for

peptidoglycans, lipoarabinomannan, and bacterial lipoproteins, while TLR4 implicated in detecting

lipopolysaccharide (LPS) and lipo-teichoic acid. Similarly, TLR5 recognizes flagellin, and TLR9 is

associated with bacterial DNA recognition. The initial identification of Toll in Drosophila as a regulator of

antifungal mechanisms suggests the potential involvement of TLRs in mammalian antifungal defence.

However, scant attention has been devoted to delineating the role of TLRs in combating fungal pathogens

in humans, despite the evolutionary link between Toll in Drosophila and antifungal mechanisms, suggesting

a plausible involvement of TLRs in mammalian antifungal defense. Notably, evidence implicates TLR4,

but not TLR2, in inducing proinflammatory cytokines in response to Aspergillus fumigatus, while its role

is purported to mediate intracellular signaling, albeit not TNF production, after stimulation of cells with

Cryptococcus neoformans. However, insights into TLR activation rules have enabled the examination of

antimicrobial peptide (AMP) interactions with TLRs, facilitating predictions regarding the

immunomodulatory capacities of diverse molecules. Despite these advancements, the specific role of TLRs

in recognizing Candida albicans, a prominent human pathogen, remains elusive, warranting further

investigation. This computational approach synthesizes recent findings elucidating the interactions between

AMPs and TLRs, delineating the structural determinants governing TLR activation, thus enabling predictive

insights into the immunomodulatory potential of diverse molecular entities.

Keywords: Toll-like receptors, antimicrobial peptide, candida infections, computational approaches,

protein-protein docking, molecular dynamics simulation, tissue engineering