Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis

Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-alpha and IL-6 but lower levels of IL-12 compared to healthy subjects. These findings suggest that there is a fundamental defect in the differentiation and maturation of dendritic cells during PTB that may compromise the antigen presentation and subsequent immune functions.