Bystander inhibition of dendritic cell differentiation by Mycobacterium tuberculosis-induced IL-10

Maria Elena Remoli, Elena Giacomini, Elisa Petruccioli, Valerie Gafa, Martina Severa, Maria Cristina Gagliardi, Elisabetta Iona, Richard Pine, Roberto Nisini, Eliana Marina Coccia

Research output: Contribution to journalArticlepeer-review

Abstract

Mycobacterium tuberculosis (Mtb) evades the immune response by impairing the functions of different antigen-presenting cells. We have recently shown that Mtb hijacks differentiation of monocytes into dendritic cells (DCs). To further characterize the mechanisms underlying this process, we investigated the consequences of inducing dendritic cell differentiation using interferon-α and granulocyte-macrophage colony-stimulating factor in the presence of supernatants (SNs) obtained from monocyte cultures treated with or without heat-inactivated Mtb. Although the SNs from control cultures do not interfere with the generation of fully differentiated DCs, monocytes stimulated with SNs from Mtb-stimulated cells (SN Mtb) remained CD14+ and poorly differentiated into CD1a+ cells. Among cytokines known to affect dendritic cell differentiation, we observed a robust production of interleukin-1Β, interleukin-6, interleukin-10 and tumor necrosis factor-α upon Mtb stimulation. However, only interleukin-10 neutralization through the addition of soluble interleukin-10 receptor reversed the inhibitory activity of SN Mtb. Accordingly, the addition of recombinant interleukin-10 was able to significantly reduce CD1a expression. The interaction of Mtb with differentiating monocytes rapidly activates p38 mitogen-activated protein kinase, signal transducer and activator of transcription pathways, which are likely involved in interleukin-10 gene expression. Taken together, our results suggest that Mtb may inhibit the differentiation of bystander non-infected monocytes into DCs through the release of interleukin-10. These results shed light on new aspects of the host-pathogen interaction, which might help to identify innovative immunological strategies to limit Mtb virulence.

Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalImmunology and Cell Biology
Volume89
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • dendritic cell differentiation
  • IL-10
  • immunoevasion strategy
  • monocyte
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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