Multinucleate giant cells and the control of chemokine secretion in response to Mycobacterium tuberculosis

Multinucleate giant cells (MGC) are characteristic of tuberculous granulomas, but their function is not well understood. In a comparative study, we investigated regulation of chemokine secretion by MGC generated using 5 microg/ml ConA and 1000 IU/ml IFN-gamma. After 72-h differentiation of MGC cultures, CXCL8, CCL2 and CCL3 concentrations were 9540+/-110 pg/ml, 11190+/-2210 pg/ml and 19440+/-440 pg/ml respectively all significantly higher than in MDM (P<0.01). There was associated increased chemokine gene expression. M.tb stimulation of MGC, MDM and monocytes increased CXCL8 secretion. M.tb increased monocyte CCL2 secretion, whereas MGC and MDM secreted CCL2 constitutively. CXCL10 secretion was induced in M.tb-stimulated MDM and constitutive in MGC. All cell types responded to M.tb with CCL3 secretion. Monocyte chemokine secretion was associated with increased gene expression, whereas M.tb-stimulated MGC principally upregulated CCL3 gene expression. In summary, differentiating MGC express genes for and secrete chemokines which regulate cell influx to sites of infection. Established MGC will contribute to cell recruitment to granuloma, but this may not depend on exposure to the pathogen.