Vitamin D, innate immunity, and sarcoidosis granulomatous inflammation: insights from mycobacterial research

Recent discoveries cast doubt on granuloma formation solely as a protective mechanism, and highlight the importance of innate immunity of the host response to pathogenic mycobacteria. Here, we briefly review evidence that mycobacterial antigens are involved in sarcoidosis pathogenesis, and explore how defects in innate immunity might contribute to the disease.

Patients with sarcoidosis demonstrate antigen-specific immune responses against mycobacterial virulence factors systemically and at sites of active involvement. Recent studies have shown the vitamin D-regulated, antimicrobial peptide cathelicidin to be important to the immune response against pathogenic mycobacteria. Given mounting evidence that mycobacterial antigens are involved in sarcoidosis pathogenesis, cathelicidin could play a role in sarcoidosis pathogenesis.

Granuloma formation is not an inevitable consequence of infection with mycobacteria. Little is known about why some individuals overcome infection by mycobacteria, whereas others develop chronic infection with granuloma formation. Here, we propose that granuloma formation might result from defects in innate immunity that prevent successful eradication of the inciting agent. Given that mycobacterial antigens have been shown to contribute to sarcoidosis pathogenesis, further research should investigate whether defects in the innate immune response to mycobacterial antigens contribute to this enigmatic disease.