Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms

Otitis media (OM) remains a prevalent and multifactorial inflammatory disease of the middle ear, especially in pediatric populations. The immune system, particularly pattern recognition receptors (PRRs), plays a central role in detecting microbial pathogens and initiating host defenses. TLR2 and TLR4 mediate bacterial clearance but exhibit subtype-specific dysregulation in chronic OM forms. NOD1, NOD2, and NLRP3 modulate intracellular pathogen sensing and inflammasome activation, while RIG-I governs antiviral immunity. C-type lectin receptors (CLRs) are emerging as modulators of both innate and adaptive responses, yet their mechanistic roles remain insufficiently explored. Cross-talk among PRRs and immune evasion by microbial biofilms contribute to chronicity and recurrence. Understanding these interactions and age- or genotype-related PRR variations may inform precision immunotherapies. This review summarizes current understanding of Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid–inducible gene I-like receptors (RLRs), and CLRs in OM pathophysiology. By elucidating the PRR-mediated signaling landscape, this review highlights the intricate PRR-mediated signaling landscape in OM, offering insights into potential therapeutic targets and future translational strategies for improving OM management.