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

Immunology. 2003 Mar;108(3):365-74. doi: 10.1046/j.1365-2567.2003.01600.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / immunology
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokines / metabolism*
  • Chemotaxis, Leukocyte / immunology
  • Gene Expression
  • Granuloma / immunology
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lung / immunology
  • Lymph Nodes / immunology
  • Macrophages, Alveolar / immunology*
  • Monocytes / immunology
  • Mycobacterium tuberculosis / immunology*
  • Neutrophils / immunology
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antigens, Bacterial
  • Chemokine CCL2
  • Chemokines
  • Interleukin-8
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta