Relative contribution of plasmacytoid DC during bacterial infections

The importance of alveolar macrophages and more recently DC in the immune response to Mycobacterium tuberculosis (MTb) has been well documented, but the relative contribution of plasmacytoid DC during bacterial infections is largely unknown. Thus, data was obtained on the contribution of pDC in acute MTb infection.

We examined whether plasmacytoid pDC are infected and/or activated by MTb, and whether they play a role in regulating bacterial clearance during acute MTb infection and if so how. We have compared these DC with myeloid DC and macrophages with respect to MTb infection. Flow cytometry analysis of CD11c populations in the lung and spleen during acute aerosol MTb infection showed no significant increase in plasmacytoid pDC; however during intravenous MTb infection the levels of plasmacytoid pDC appear to increase 43 days after infection. Lung CD4+ T cells increase after day 8 post aerosol infection as previously published by others. In addition, depletion of plasmacytoid pDC in vivo during acute intravenous MTb infection suggested that this DC subset plays a minimal role in regulating bacterial clearance during the primary immune response. In vitro MTb infection of BM myeloid DC and BM macrophages induced the pro-inflammatory cytokines IL-12p40 and TNF, as previously reported by others. In contrast, in vitro MTb infection of plasmacytoid pDC did not induce any detectable levels of cytokine. However, CpG stimulation of plasmacytoid pDC induced the cytokines IL-12p40, IL-12p70, TNF and IFN-alpha. Our data suggests that at this stage of infection plasmacytoid pDC may play only a limited role in protection against MTb infection. Our data however, does not address the possibility that plasmacytoid pDC may play a role during chronic infection when death of bacteria may be greater i.e. during memory responses or following antibiotic treatment, which may give release of un-methylated CpG DNA that could potentially activate plasmacytoid pDC via TLR-9, or in response to the virulent strain of MTB HN878 as described by Manca et al., 2001. Since in the mouse CpG stimulates IL-12 and TNF production by macrophages, myeloid and plasmacytoid DC, we also investigated a possible protective role for CpG in protection against MTB infection. We found that administration to mice with CpG could play a role in protection although this was very dependent on the time of administration, the dose of MTb used and the strain of mouse.

The in vitro studies on infections with Mycobacterium tuberculosis (MTb) of macrophages and DC have been discontinued.

• stimulus type
• mycobacterium tuberculosis

• cell type
• myeloid dendritic cell,
• plasmacytoid dendritic cell,
• macrophage

• molecule type
• Interleukin-12 p70,
• CpG,
• Tumor necrosis factor,
• Interleukin-12 cytokine,
• Toll like receptor 9,
• interferon alpha,
• Interleukin-12 p40,
• CD4,
• CD11c

• organ type
• lung,
• human bone marrow

• organism type
• Mus musculus

created over 15 years ago (2 March 2009)    last modified over 12 years ago (20 August 2012)   [ RDF ]   [ RelFinder ]