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CD8+ DC, but Not CD8(-)DC, isolated from BCG-infected mice reduces pathological reactions induced by mycobacterial challenge infection.

Gao X, Wang S, Fan Y, Bai H, Yang J, Yang X - PLoS ONE (2010)

Bottom Line: The adoptive transfer of the CD8alpha(-)DC from the infected mice (iCD8(-) DC) not only failed to reduce bacterial growth, but enhanced inflammation characterized by diffuse heavy cellular infiltration.Notably, iCD8(-) DC produced significantly higher levels of IL-10 than iCD8+ DC and promoted more Th2 cytokine responses in in vitro DC-T cell co-culture and in vivo adoptive transfer experiments.The data indicate that in vivo BCG-primed CD8+ DC is the dominant DC subset in inducing protective immunity especially for reducing pathological reactions in infected tissues.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Infection and Immunity, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

ABSTRACT

Background: Tuberculosis is a mycobacterial infection causing worldwide public health problems but the available vaccine is far from ideal. Type-1 T cell immunity has been shown to be critical for host defence against tuberculosis infection, but the role of dendritic cell (DC) subsets in pathogenesis of mycobacterial infection remains unclear.

Methodology/principal findings: We examined the effectiveness of dendritic cell (DC) subsets in BCG-infected mice in generating immune responses beneficial for pathogen clearance and reduction of pathological reactions in the tissues following challenge infection. Our data showed that only the adoptive transfer of the subset of CD8alpha+ DC isolated from infected mice (iCD8+ DC) generated significant protection, demonstrated by less mycobacterial growth and pathological changes in the lung and liver tissues in iCD8+ DC recipients than sham-treated control mice. The adoptive transfer of the CD8alpha(-)DC from the infected mice (iCD8(-) DC) not only failed to reduce bacterial growth, but enhanced inflammation characterized by diffuse heavy cellular infiltration. Notably, iCD8(-) DC produced significantly higher levels of IL-10 than iCD8+ DC and promoted more Th2 cytokine responses in in vitro DC-T cell co-culture and in vivo adoptive transfer experiments.

Conclusions/significance: The data indicate that in vivo BCG-primed CD8+ DC is the dominant DC subset in inducing protective immunity especially for reducing pathological reactions in infected tissues. The finding has implications for the rational improvement of the prophylactic and therapeutic approaches for controlling tuberculosis infection and related diseases.

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Related in: MedlinePlus

Significantly milder pathological changes in recipients of iCD8 +DC following intravenous challenge infection.Mice were treated/challenged as described in the legend to Figure 4 and analyzed for histopathological changes in lung and liver at day 21 post challenge infection by H&E staining. Low magnification(x20) and high magnification (x100) were shown respectively. Green arrows indicate typical epithelioid cells.
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pone-0009281-g005: Significantly milder pathological changes in recipients of iCD8 +DC following intravenous challenge infection.Mice were treated/challenged as described in the legend to Figure 4 and analyzed for histopathological changes in lung and liver at day 21 post challenge infection by H&E staining. Low magnification(x20) and high magnification (x100) were shown respectively. Green arrows indicate typical epithelioid cells.

Mentions: More remarkably, further histopathological analysis (Figure 5) showed that the recipient of iCD8+ DC only had mild pathological changes in the lung and liver. In contrast, the sham-treated mice and the recipients of iCD8− DC showed much more severe pathological inflammatory reactions. Interestingly, although both sham-treated mice and iCD8− DC recipients showed severe pathological reactions, their pattern of changes were different. Sham-treated mice showed multiple granulomas in both lung and liver tissues, characterized by dominant epithelioid cells (indicated by green arrows in Fig. 5) at centre with surrounding lymphocytes, neutrophil and monocytes in peribronchial and perivascular areas (lung) and peri-central vein areas of the hepatic lobules (liver). Multinucleate giant cells were also observed in the sham-treated mice. In contrast, the inflammation in iCD8− DC recipients was diffused without notable granulomas and lack of typical epitheloid cells. The infiltrating cells in these mice were mainly neutrophils and mononuclear cell.


CD8+ DC, but Not CD8(-)DC, isolated from BCG-infected mice reduces pathological reactions induced by mycobacterial challenge infection.

Gao X, Wang S, Fan Y, Bai H, Yang J, Yang X - PLoS ONE (2010)

Significantly milder pathological changes in recipients of iCD8 +DC following intravenous challenge infection.Mice were treated/challenged as described in the legend to Figure 4 and analyzed for histopathological changes in lung and liver at day 21 post challenge infection by H&E staining. Low magnification(x20) and high magnification (x100) were shown respectively. Green arrows indicate typical epithelioid cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2823775&req=5

pone-0009281-g005: Significantly milder pathological changes in recipients of iCD8 +DC following intravenous challenge infection.Mice were treated/challenged as described in the legend to Figure 4 and analyzed for histopathological changes in lung and liver at day 21 post challenge infection by H&E staining. Low magnification(x20) and high magnification (x100) were shown respectively. Green arrows indicate typical epithelioid cells.
Mentions: More remarkably, further histopathological analysis (Figure 5) showed that the recipient of iCD8+ DC only had mild pathological changes in the lung and liver. In contrast, the sham-treated mice and the recipients of iCD8− DC showed much more severe pathological inflammatory reactions. Interestingly, although both sham-treated mice and iCD8− DC recipients showed severe pathological reactions, their pattern of changes were different. Sham-treated mice showed multiple granulomas in both lung and liver tissues, characterized by dominant epithelioid cells (indicated by green arrows in Fig. 5) at centre with surrounding lymphocytes, neutrophil and monocytes in peribronchial and perivascular areas (lung) and peri-central vein areas of the hepatic lobules (liver). Multinucleate giant cells were also observed in the sham-treated mice. In contrast, the inflammation in iCD8− DC recipients was diffused without notable granulomas and lack of typical epitheloid cells. The infiltrating cells in these mice were mainly neutrophils and mononuclear cell.

Bottom Line: The adoptive transfer of the CD8alpha(-)DC from the infected mice (iCD8(-) DC) not only failed to reduce bacterial growth, but enhanced inflammation characterized by diffuse heavy cellular infiltration.Notably, iCD8(-) DC produced significantly higher levels of IL-10 than iCD8+ DC and promoted more Th2 cytokine responses in in vitro DC-T cell co-culture and in vivo adoptive transfer experiments.The data indicate that in vivo BCG-primed CD8+ DC is the dominant DC subset in inducing protective immunity especially for reducing pathological reactions in infected tissues.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Infection and Immunity, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

ABSTRACT

Background: Tuberculosis is a mycobacterial infection causing worldwide public health problems but the available vaccine is far from ideal. Type-1 T cell immunity has been shown to be critical for host defence against tuberculosis infection, but the role of dendritic cell (DC) subsets in pathogenesis of mycobacterial infection remains unclear.

Methodology/principal findings: We examined the effectiveness of dendritic cell (DC) subsets in BCG-infected mice in generating immune responses beneficial for pathogen clearance and reduction of pathological reactions in the tissues following challenge infection. Our data showed that only the adoptive transfer of the subset of CD8alpha+ DC isolated from infected mice (iCD8+ DC) generated significant protection, demonstrated by less mycobacterial growth and pathological changes in the lung and liver tissues in iCD8+ DC recipients than sham-treated control mice. The adoptive transfer of the CD8alpha(-)DC from the infected mice (iCD8(-) DC) not only failed to reduce bacterial growth, but enhanced inflammation characterized by diffuse heavy cellular infiltration. Notably, iCD8(-) DC produced significantly higher levels of IL-10 than iCD8+ DC and promoted more Th2 cytokine responses in in vitro DC-T cell co-culture and in vivo adoptive transfer experiments.

Conclusions/significance: The data indicate that in vivo BCG-primed CD8+ DC is the dominant DC subset in inducing protective immunity especially for reducing pathological reactions in infected tissues. The finding has implications for the rational improvement of the prophylactic and therapeutic approaches for controlling tuberculosis infection and related diseases.

Show MeSH
Related in: MedlinePlus