Endogenous Hypersensitivity Infection: A Unifying Framework for Cutibacterium acnes-Associated Sarcoidosis

Area of Science:

• Immunology
• Microbiology
• Pathology

Background:

• Sarcoidosis is an immune-mediated granulomatous disease with an unknown cause.
• Cutibacterium acnes (C. acnes), a common commensal bacterium, is increasingly implicated as a potential trigger.

Purpose of the Study:

• To propose the concept of Endogenous Hypersensitivity Infection (EHI) to explain sarcoidosis etiology.
• To reframe sarcoidosis as a disorder of host-commensal homeostasis.

Main Methods:

• Review of microbiological, immunopathological, and pathological evidence.
• Integration of data on C. acnes detection in sarcoid granulomas.
• Synthesis of mechanistic basis for EHI.

Main Results:

• C. acnes is frequently detected in sarcoid granulomas, suggesting latent persistence and reactivation.
• The EHI concept explains how C. acnes reactivation can trigger Th1-dominant hypersensitivity.
• EHI bridges infection and autoimmunity, reframing sarcoidosis.

Conclusions:

• Sarcoidosis may result from immune tolerance failure to C. acnes, leading to EHI.
• The EHI paradigm offers a unifying framework for sarcoidosis and related inflammatory disorders.
• This model reinterprets sarcoidosis as a disruption of host-commensal balance.