Vitamin D Dependent Pathway Key in Immunity Against TB

T cells release interferon-γ to induce antimicrobial activities by human macrophages

THURSDAY, Oct. 13 (HealthDay News) -- Interferon-γ (IFN-γ) released by T cells induces multiple macrophage responses to Mycobacterium tuberculosis in in a vitamin D-dependent pathway, according to a study published in the Oct. 12 issue of Science Translational Medicine.

Mario Fabri, from the University of California in Los Angeles, and colleagues investigated the mechanisms that control antimicrobial activity in human macrophages, and the role of vitamin D in the antimicrobial response.

The investigators found that T cells release IFN-γ to induce a number of activities in human macrophages via a vitamin D-dependent pathway. These include autophagy, phagosomal maturation, the production of antimicrobial peptides (including cathelicidin), and antimicrobial activity. Human macrophages cultured in sera that contain sufficient concentrations of vitamin D exhibited an antimicrobial pathway based on IFN-γ, but this was not seen in sera from African-Americans, who have lower amounts of vitamin D and increased susceptibility to tuberculosis. IFN-γ-induced autophagy, phagosome-lysosome fusion, antimicrobial peptide expression, and antimicrobial activity were all restored when the vitamin D-deficient serum was supplemented in vitro with 25-hydroxy vitamin D3.

"These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection," the authors write.

Two authors disclosed financial ties to DiaSorin Inc., producers of a vitamin D assay.

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