25-hydroxyvitamin-d-2 and Granuloma

Control of human tuberculosis (TB) requires induction and maintenance of both macrophage and T cell effector functions. We demonstrate that pulmonary TB patients with a vitamin D deficiency had significantly reduced local levels of the vitamin D-inducible antimicrobial peptide LL-37 in granulomatous lesions compared to distal parenchyma from the infected lung. Instead, TB lesions were abundant in CD3(+) T cells and FoxP3(+) regulatory T cells as well as IgG-secreting CD20(+) B cells, particularly in sputum-smear positive patients with cavitary TB. Mycobacteria-specific serum IgG titers were also elevated in patients with active TB. An up-regulation of the B cell stimulatory cytokine IL-21 correlated with mRNA expression of CD20, total IgG and also IL-10 in the TB lesions. Altogether, vitamin D-deficient TB patients expressed a weak antimicrobial response but an IL-21 associated expansion of IgG-secreting B cells combined with a rise in FoxP3(+) regulatory T cells at the local site of infection.

Topics: 25-Hydroxyvitamin D 2; Adult; Antigens, CD20; Antimicrobial Cationic Peptides; B-Lymphocytes; Calcifediol; Cathelicidins; Female; Forkhead Transcription Factors; Granuloma; Humans; Immunoglobulin G; Interleukin-10; Interleukins; Lung; Male; Middle Aged; Mycobacterium tuberculosis; T-Lymphocytes, Regulatory; Tuberculosis, Pulmonary; Vitamin D Deficiency