Leishmania donovani infection initiates T cell-independent chemokine responses, which are subsequently amplified in a T cell-dependent manner

Eur J Immunol. 1999 Jan;29(1):203-14. doi: 10.1002/(SICI)1521-4141(199901)29:01<203::AID-IMMU203>3.0.CO;2-B.

Abstract

Control of Leishmania donovani infection in immunocompetent mice is associated with hepatic inflammation and granuloma formation, both of which are absent in severe combined immunodeficient (scid) mice. In both BALB/c and scid mice, L. donovani infection induced a rapid hepatic accumulation of mRNA encoding macrophage inflammatory protein-1alpha (MIP-(1alpha), monocyte chemoattractant protein-1 (MCP-1) and interferon-gamma inducible protein-10 (gammaIP-10). This response was not preceded by increased IL-4 production in either strain, unlike that reported in other infectious disease models. Interestingly, only gammaIP-10 mRNA was maintained at elevated levels throughout the first 7 days of infection, by mechanisms involving CD4+ and CD8+ T cells, and CD4+CD8+ cells not activated in scid mice. By in vivo depletion and reconstitution of scid mice it was demonstrated that T cells regulate the expression of all three chemokines studied, while they themselves only produce gammaIP-10 in appreciable quantities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL10
  • Chemokines / biosynthesis*
  • Chemokines / genetics*
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / genetics
  • Female
  • Gene Expression Regulation
  • Granuloma / etiology
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Kinetics
  • Leishmania donovani / immunology*
  • Leishmaniasis, Visceral / genetics*
  • Leishmaniasis, Visceral / immunology*
  • Liver / immunology
  • Liver Diseases / etiology
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Models, Biological
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology*

Substances

  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CXC
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma