Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells

A. Giuliani, S. P. Prete, G. Graziani, A. Aquino, A. Balduzzi, M. Sugita, M. B. Brenner, E. Iona, L. Fattorini, G. Orefici, Steven A. Porcelli, E. Bonmassar

Research output: Contribution to journalArticle

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Abstract

Nonpeptide antigens (including glycolipids of microbial origin) can be presented to T cells by CD1 molecules expressed on monocyte-derived dendritic cells. These HLA unrestricted responses appear to play a role in host immunity against Mycobacterium tuberculosis and other pathogenic bacteria. It is known that vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) has limited efficacy in many clinical settings, although the reasons for its inadequacy remain unclear. Here we have investigated the influence of BCG on the induction of CD1b on human monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is believed to be the principal inducer of this antigen-presenting molecule. Although BCG alone led to a slight induction of CD1b expression, this agent reduced markedly the ability of GM-CSF to induce high levels of CD1b that were typically observed in uninfected cells. Inhibition of CD1b expression in BCG-infected monocytes was apparent at both the mRNA transcript and CD1b protein levels. Down-regulation of CD1b expression by BCG was mediated, at least in part, by one or more soluble factors and could not be reversed with high concentrations of GM-CSF or a variety of other cytokines. The present results suggest that BCG could diminish the efficiency of CD1-restricted T-cell responses against nonpeptide mycobacterial antigens by reducing CD1 expression on antigen-presenting cells. These findings have potential implications for understanding the nature of the immune response elicited by BCG in humans and suggest potential strategies that could be important for the development of better vaccines for the prevention of tuberculosis.

Original languageEnglish (US)
Pages (from-to)7461-7470
Number of pages10
JournalInfection and Immunity
Volume69
Issue number12
DOIs
StatePublished - 2001

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Mycobacterium bovis
Bacillus
Granulocyte-Macrophage Colony-Stimulating Factor
Monocytes
CD1 Antigens
Tuberculosis Vaccines
T-Lymphocytes
Antigens
Glycolipids
Antigen-Presenting Cells
In Vitro Techniques
Mycobacterium tuberculosis
Dendritic Cells
Immunity
Vaccination
Down-Regulation
Cytokines
Bacteria
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Immunology

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Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells. / Giuliani, A.; Prete, S. P.; Graziani, G.; Aquino, A.; Balduzzi, A.; Sugita, M.; Brenner, M. B.; Iona, E.; Fattorini, L.; Orefici, G.; Porcelli, Steven A.; Bonmassar, E.

In: Infection and Immunity, Vol. 69, No. 12, 2001, p. 7461-7470.

Research output: Contribution to journalArticle

Giuliani, A, Prete, SP, Graziani, G, Aquino, A, Balduzzi, A, Sugita, M, Brenner, MB, Iona, E, Fattorini, L, Orefici, G, Porcelli, SA & Bonmassar, E 2001, 'Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells', Infection and Immunity, vol. 69, no. 12, pp. 7461-7470. https://doi.org/10.1128/IAI.69.12.7461-7470.2001
Giuliani, A. ; Prete, S. P. ; Graziani, G. ; Aquino, A. ; Balduzzi, A. ; Sugita, M. ; Brenner, M. B. ; Iona, E. ; Fattorini, L. ; Orefici, G. ; Porcelli, Steven A. ; Bonmassar, E. / Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells. In: Infection and Immunity. 2001 ; Vol. 69, No. 12. pp. 7461-7470.
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AU - Aquino, A.

AU - Balduzzi, A.

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AU - Porcelli, Steven A.

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