title: Pulmonary tuberculosis patients with a vitamin D deficiency demonstrate low local expression of the antimicrobial peptide LL-37 but enhanced FoxP3+ regulatory T cells and IgG-secreting cells.
abstract: 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.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Sayma
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Rehn
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jubayer
authors.initials: J
authors.lastname: Rahman
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: susanna.brighenti@ki.se.
authors.forename: Susanna
authors.initials: S
authors.lastname: Brighenti
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D000328:Adult; D018951:Antigens, CD20 / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D002112:Calcifediol / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology*; D014808:Vitamin D Deficiency / Q000150:complications*; D054804:Cathelicidins; D000098546:Interleukin-21
chemical_list: D018951:Antigens, CD20; D023181:Antimicrobial Cationic Peptides; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D007074:Immunoglobulin G; D007378:Interleukins; D016753:Interleukin-10; D015652:25-Hydroxyvitamin D 2; D000098546:Interleukin-21; D002112:Calcifediol; D054804:Cathelicidins
keywords: Antimicrobial peptide; B cell; Human; Lung; T cell; Tuberculosis