Mycobacteria-infected bystander macrophages trigger maturation of dendritic cells and enhance their ability to mediate HIV transinfection

Research output: Contribution to journalArticle

Abstract

Synergistic interplay between Mycobacterium tuberculosis (Mtb) and HIV in coinfected ind-ividuals leads to the acceleration of both tuberculosis and HIVdisease. Mtb, as well as HIV, may modulate the function of many immune cells, including DCs. To dissect the bystander impact of Mfs infected with Mtb on DC functionality, we here investigated changes in DC phenotype, cytokine profiles, and HIV-1 transinfecting ability. An in vitro system was used in which human monocyte-derived DCs were exposed to soluble factors released by Mfs infected with mycobacteria, including virulent clinical Mtb isolates and nonvirulent BCG. Soluble factors secreted from Mtb-infected Mfs, and to a lesser extent BCG-infected Mfs, resulted in the production of proinflammatory cytokines and partial upregulation of DC maturation markers. Interestingly, the HIV-1 transinfecting ability of DCs was enhanced upon exposure to soluble factors released by Mtb-infected Mfs. In summary, our study shows that DCs exposed to soluble factors released by mycobacteria-infected Mfs undergo maturation and display an augmented ability to transmit HIV-1 in trans. These findings highlight the important role of bystander effects during the course of MtbHIV coinfection and suggest that Mtb-infected Mfs may contribute to an environment that supports DC-mediated spread and amplification of HIV in coinfected individuals.

Details

Authors
  • Jolanta Mazurek
  • Lech Ignatowicz
  • Gunilla Kallenius
  • Marianne Jansson
  • Andrzej Pawlowski
Organisations
External organisations
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • coinfection center dot dendritic cell center dot HIV-1 center dot, macrophage center dot Mycobacterium tuberculosis
Original languageEnglish
Pages (from-to)1192-1202
JournalEuropean Journal of Immunology
Volume42
Issue number5
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes