Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations: focus on gammadelta cells.
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). gammadelta and T helper type 1 (Th1) alphabeta 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 gammadelta 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 gammadelta 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 gammadelta T cells, as well as in the regulation of gammadelta function.
Ferrero
Elisabetta
E
Laboratory of Tumour Immunology, Università Vita e Salute, Scientific Institute H San Raffaele, Via Olgettina 60, I-20132 Milan, Italy. e.ferrero@hsr.it
Biswas
Priscilla
P
Vettoretto
Katuscia
K
Ferrarini
Marina
M
Uguccioni
Mariagrazia
M
Piali
Luca
L
Leone
Biagio Eugenio
BE
Moser
Bernhard
B
Rugarli
Claudio
C
Pardi
Ruggero
R
D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015870:Gene Expression; D006099:Granuloma / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000942:Antigens, Bacterial; D018932:Chemokine CCL2; D018925:Chemokines; D016209:Interleukin-8; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta