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Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T

B Neumeister1, M Faigle, D Spitznagel

  • 1Abteilung Transfusionsmedizin, AG Infektionsbiologie, Universitätsklinikum Tübingen, 72076, Tübingen, Germany. Birgid.Neumeister@med.uni-tuebingen.de

Cellular and Molecular Life Sciences : CMLS
|March 5, 2005
PubMed

Insights

Legionella pneumophila infection significantly reduces MHC class I expression on monocytes. This immune evasion strategy involves absorbing ER chaperones, hindering T-cell responses against Legionnaires' disease.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Legionella pneumophila is an intracellular bacterium causing Legionnaires' disease.
  • It infects alveolar macrophages and resides within an endoplasmic reticulum (ER)-like compartment.

Purpose of the Study:

  • To investigate the effect of L. pneumophila intracellular multiplication on host cell MHC class I expression.
  • To elucidate the mechanism behind changes in MHC class I expression.
  • To determine the impact of altered MHC class I on immune cell interactions.

Main Methods:

  • Infection of monocytes with L. pneumophila.
  • Analysis of MHC class I expression levels on infected cells.
  • Investigation of ER-resident chaperone interactions with the bacterium.
  • Assessment of immune cell stimulation and cytotoxicity assays.

Main Results:

  • Intracellular multiplication of L. pneumophila led to a significant decrease in MHC class I expression on infected monocytes.
  • L. pneumophila was found to absorb ER-resident chaperones (calnexin, BiP) essential for MHC class I complex formation.
  • Reduced MHC class I expression inhibited stimulation of allogeneic blood mononuclear cells.
  • Cytotoxicity of autologous natural killer cells against infected monocytes was not enhanced.

Conclusions:

  • L. pneumophila actively downregulates MHC class I expression on infected monocytes.
  • This downregulation is mediated by the absorption of essential ER chaperones.
  • Reduced MHC class I expression represents a potential immune escape mechanism employed by L. pneumophila to evade host immune responses.

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