Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations: focus on γδ cells

E Ferrero, P Biswas, K Vettoretto, M Ferrarini… - …, 2003 - Wiley Online Library
E Ferrero, P Biswas, K Vettoretto, M Ferrarini, M Uguccioni, L Piali, BE Leone, B Moser
Immunology, 2003Wiley Online Library
Granuloma is a typical feature of tuberculosis. We evaluated the chemotaxis of selected
human leucocyte subsets induced by macrophages incubated with Mycobacterium
tuberculosis (MT)‐derived products in vitro. The release of monocyte chemotactic protein 1
(MCP‐1) and interleukin‐8 (IL‐8) correlated with the specific induction of strong chemotaxis
towards monocytes and polymorphonuclear leucocytes (PMNs). γδ and T helper type 1
(Th1) αβ lymphocytes were chemoattracted, while T‐resting, IL‐2‐activated and Th2 …
Summary
Granuloma is a typical feature of tuberculosis. We evaluated the chemotaxis of selected human leucocyte subsets induced by macrophages incubated with Mycobacterium tuberculosis (MT)‐derived products in vitro. The release of monocyte chemotactic protein 1 (MCP‐1) and interleukin‐8 (IL‐8) correlated with the specific induction of strong chemotaxis towards monocytes and polymorphonuclear leucocytes (PMNs). γδ and T helper type 1 (Th1) αβ lymphocytes were chemoattracted, while T‐resting, IL‐2‐activated and Th2 lymphocytes were unaffected. Activation with mycobacterium‐derived, phosphate‐containing components, modulated the chemokine receptor profile of γδ T lymphocytes as well as their pattern of cyto‐chemokine production, disclosing a potential for their active participation in granuloma formation. In particular, CXCR3 and IP‐10, which we found to be released by MT‐pulsed alveolar macrophages, seem to represent the receptor–counter‐receptor pair implicated in the chemotaxis of γδ lymphocytes. Immunohistochemical analysis and in situ hybridization revealed the in vivo presence of IL‐8, MCP‐1 and IL‐10 in lymph node and lung tuberculous granulomas. Our results underscore the role of MT extracts in the induction of macrophage‐derived chemokines responsible for the orchestrated recruitment of PMNs, monocytes, and Th1 and γδ T cells, as well as in the regulation of γδ function.
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