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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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Adoptive transfer of iCD8+DC, but not iCD8− DC, reduced bacterial growths in recipients following either i.v. or i.n. challenge infection.DC subsets were sorted from BCG-infected (i.v.) mice or naïve mice and adoptively transferred to syngeneic recipients (C57BL/6, n = 4/group) by i.v. (A&B, 5×105 DC/mouse) or i.n. routes (C, 2×105 DC/mouse). Mice were challenged with BCG through i.v. (A&B) or i.n. (C) routes, respectively, as described in Materials and Methods. All mice were sacrificed at day 21 post challenge infection. Homogenized lung or liver tissues were measured for BCG CFU. The CFUs of BCG were converted to logarithmic values and presented as mean±SD of each group. One representative experiment of three independent experiments is shown. * p<0.05;**, p<0.01.
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pone-0009281-g004: Adoptive transfer of iCD8+DC, but not iCD8− DC, reduced bacterial growths in recipients following either i.v. or i.n. challenge infection.DC subsets were sorted from BCG-infected (i.v.) mice or naïve mice and adoptively transferred to syngeneic recipients (C57BL/6, n = 4/group) by i.v. (A&B, 5×105 DC/mouse) or i.n. routes (C, 2×105 DC/mouse). Mice were challenged with BCG through i.v. (A&B) or i.n. (C) routes, respectively, as described in Materials and Methods. All mice were sacrificed at day 21 post challenge infection. Homogenized lung or liver tissues were measured for BCG CFU. The CFUs of BCG were converted to logarithmic values and presented as mean±SD of each group. One representative experiment of three independent experiments is shown. * p<0.05;**, p<0.01.

Mentions: To further examine the functional difference of the DC subsets, we adoptively transferred the iCD8+ DC and iCD8− DC subsets and tested protection in the recipients of the different DC subsets to challenge infection. DC subsets were purified from BCG-infected mice at day 21 post immunization and were adoptively transferred i.v. to naïve C57BL/6 mice. At 7 days after cell transfer, the recipient mice were challenged i.v. with BCG. Mice that received PBS (sham treatment) or DC subsets from naive mice with the same challenge infection were used as controls. Twenty-one days after challenge infection, mice were sacrificed and the bacterial loads in the lung and liver were measured. As shown in Fig. 4, a significant reduction in tissue bacterial loads were observed in the mouse group receiving iCD8+ DC compared with the mice without DC transfer (sham treated control mice). In contrast, although the recipients of iCD8− DC also appeared to have a trend of lower CFU in the lung and liver compared to PBS controls, the differences were not statistically significant. As controls, the recipients of either DC subsets from naïve mice (nCD8+ DC or nCD8− DC) showed comparable levels of bacterial loads with the PBS treated control mice, therefore not generating protection.


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)

Adoptive transfer of iCD8+DC, but not iCD8− DC, reduced bacterial growths in recipients following either i.v. or i.n. challenge infection.DC subsets were sorted from BCG-infected (i.v.) mice or naïve mice and adoptively transferred to syngeneic recipients (C57BL/6, n = 4/group) by i.v. (A&B, 5×105 DC/mouse) or i.n. routes (C, 2×105 DC/mouse). Mice were challenged with BCG through i.v. (A&B) or i.n. (C) routes, respectively, as described in Materials and Methods. All mice were sacrificed at day 21 post challenge infection. Homogenized lung or liver tissues were measured for BCG CFU. The CFUs of BCG were converted to logarithmic values and presented as mean±SD of each group. One representative experiment of three independent experiments is shown. * p<0.05;**, p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2823775&req=5

pone-0009281-g004: Adoptive transfer of iCD8+DC, but not iCD8− DC, reduced bacterial growths in recipients following either i.v. or i.n. challenge infection.DC subsets were sorted from BCG-infected (i.v.) mice or naïve mice and adoptively transferred to syngeneic recipients (C57BL/6, n = 4/group) by i.v. (A&B, 5×105 DC/mouse) or i.n. routes (C, 2×105 DC/mouse). Mice were challenged with BCG through i.v. (A&B) or i.n. (C) routes, respectively, as described in Materials and Methods. All mice were sacrificed at day 21 post challenge infection. Homogenized lung or liver tissues were measured for BCG CFU. The CFUs of BCG were converted to logarithmic values and presented as mean±SD of each group. One representative experiment of three independent experiments is shown. * p<0.05;**, p<0.01.
Mentions: To further examine the functional difference of the DC subsets, we adoptively transferred the iCD8+ DC and iCD8− DC subsets and tested protection in the recipients of the different DC subsets to challenge infection. DC subsets were purified from BCG-infected mice at day 21 post immunization and were adoptively transferred i.v. to naïve C57BL/6 mice. At 7 days after cell transfer, the recipient mice were challenged i.v. with BCG. Mice that received PBS (sham treatment) or DC subsets from naive mice with the same challenge infection were used as controls. Twenty-one days after challenge infection, mice were sacrificed and the bacterial loads in the lung and liver were measured. As shown in Fig. 4, a significant reduction in tissue bacterial loads were observed in the mouse group receiving iCD8+ DC compared with the mice without DC transfer (sham treated control mice). In contrast, although the recipients of iCD8− DC also appeared to have a trend of lower CFU in the lung and liver compared to PBS controls, the differences were not statistically significant. As controls, the recipients of either DC subsets from naïve mice (nCD8+ DC or nCD8− DC) showed comparable levels of bacterial loads with the PBS treated control mice, therefore not generating protection.

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