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Host immunity in the protective response to vaccination with heat-killed Burkholderia mallei.

Whitlock GC, Lukaszewski RA, Judy BM, Paessler S, Torres AG, Estes DM - BMC Immunol. (2008)

Bottom Line: Our results demonstrated that mice depleted of either B cells, TNF-alpha or IFN-gamma exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route.The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model.The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-gamma and TNF-alpha in protection following HK vaccination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA. gcwhilo@utmb.edu

ABSTRACT

Background: We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection.

Results: While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-alpha or IFN-gamma exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally.

Conclusion: The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-gamma and TNF-alpha in protection following HK vaccination.

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Percentage of survival among C57BL/6 B-cell (μMT), CD4 T-cell (CD4-/-) and CD8 T-cell (CD8-/-)-deficient, HK-vaccinated mice. Two weeks post vaccination, mice were challenged with 2 × 107 CFU/100 μl of live B. mallei by intraperitoneal injection. B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to that of the wild-type mice with a MST of 35.5 days (n = 6). CD4-/- and CD8-/- mice resulted in 60% (p = 0.1343) and 0% reduced survival, respectively (n = 5).
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Figure 3: Percentage of survival among C57BL/6 B-cell (μMT), CD4 T-cell (CD4-/-) and CD8 T-cell (CD8-/-)-deficient, HK-vaccinated mice. Two weeks post vaccination, mice were challenged with 2 × 107 CFU/100 μl of live B. mallei by intraperitoneal injection. B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to that of the wild-type mice with a MST of 35.5 days (n = 6). CD4-/- and CD8-/- mice resulted in 60% (p = 0.1343) and 0% reduced survival, respectively (n = 5).

Mentions: To dissect the cellular basis for protection mediated by HK vaccination, 13 days after immunization with HK bacteria (day -1), and at day of challenge, mice were dosed with antibodies to deplete CD4+, CD8+ or B220+ cells. Antibody depletion of CD4+, CD8+, or B220+ cells in these mice was confirmed by flow cytometric analysis with depletion efficiencies for CD4, CD8, and B220 populations at 99.7%, 96%, and 95%, respectively, relative to mice treated with isotype control monoclonal antibodies (data not shown). Our results demonstrated decreased survival rates in B220 (p = 0.3418), CD4+ (p = 0.5417) and CD8+ (p = 0.4684) antibody depleted mice, compared to isotype control antibody, a finding that indicated a possible role for vaccine induced antibody production. When challenged with 2 × 107 CFU/mouse by the i.p. route, loss of T cells resulted in reduced survival (50%) relative to the non-specific isotype control (Fig. 2). In contrast to the loss of T cells, depletion of B220+ cells resulted in 100% mortality relative to the non-specific isotype control (Fig. 2). To further evaluate the necessity of these effector cells in providing protection following HK vaccination, relatively resistant C57BL/6 mice, deficient in mature B-cells (μMT), CD4 T-cells (CD4-/-) or CD8 T-cells (CD8-/-) were subjected to an identical HK vaccination and challenge regimen. Mature, B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to the wild-type mice with an MST of 35.5 days (Fig. 3). CD4-/- and CD8-/- mice exhibited a 60% (p = 0.1343) and 0% reduced survival, respectively (Fig. 3).


Host immunity in the protective response to vaccination with heat-killed Burkholderia mallei.

Whitlock GC, Lukaszewski RA, Judy BM, Paessler S, Torres AG, Estes DM - BMC Immunol. (2008)

Percentage of survival among C57BL/6 B-cell (μMT), CD4 T-cell (CD4-/-) and CD8 T-cell (CD8-/-)-deficient, HK-vaccinated mice. Two weeks post vaccination, mice were challenged with 2 × 107 CFU/100 μl of live B. mallei by intraperitoneal injection. B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to that of the wild-type mice with a MST of 35.5 days (n = 6). CD4-/- and CD8-/- mice resulted in 60% (p = 0.1343) and 0% reduced survival, respectively (n = 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562362&req=5

Figure 3: Percentage of survival among C57BL/6 B-cell (μMT), CD4 T-cell (CD4-/-) and CD8 T-cell (CD8-/-)-deficient, HK-vaccinated mice. Two weeks post vaccination, mice were challenged with 2 × 107 CFU/100 μl of live B. mallei by intraperitoneal injection. B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to that of the wild-type mice with a MST of 35.5 days (n = 6). CD4-/- and CD8-/- mice resulted in 60% (p = 0.1343) and 0% reduced survival, respectively (n = 5).
Mentions: To dissect the cellular basis for protection mediated by HK vaccination, 13 days after immunization with HK bacteria (day -1), and at day of challenge, mice were dosed with antibodies to deplete CD4+, CD8+ or B220+ cells. Antibody depletion of CD4+, CD8+, or B220+ cells in these mice was confirmed by flow cytometric analysis with depletion efficiencies for CD4, CD8, and B220 populations at 99.7%, 96%, and 95%, respectively, relative to mice treated with isotype control monoclonal antibodies (data not shown). Our results demonstrated decreased survival rates in B220 (p = 0.3418), CD4+ (p = 0.5417) and CD8+ (p = 0.4684) antibody depleted mice, compared to isotype control antibody, a finding that indicated a possible role for vaccine induced antibody production. When challenged with 2 × 107 CFU/mouse by the i.p. route, loss of T cells resulted in reduced survival (50%) relative to the non-specific isotype control (Fig. 2). In contrast to the loss of T cells, depletion of B220+ cells resulted in 100% mortality relative to the non-specific isotype control (Fig. 2). To further evaluate the necessity of these effector cells in providing protection following HK vaccination, relatively resistant C57BL/6 mice, deficient in mature B-cells (μMT), CD4 T-cells (CD4-/-) or CD8 T-cells (CD8-/-) were subjected to an identical HK vaccination and challenge regimen. Mature, B-cell-deficient mice demonstrated a 50% decreased survival (p = 0.0888) compared to the wild-type mice with an MST of 35.5 days (Fig. 3). CD4-/- and CD8-/- mice exhibited a 60% (p = 0.1343) and 0% reduced survival, respectively (Fig. 3).

Bottom Line: Our results demonstrated that mice depleted of either B cells, TNF-alpha or IFN-gamma exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route.The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model.The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-gamma and TNF-alpha in protection following HK vaccination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA. gcwhilo@utmb.edu

ABSTRACT

Background: We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection.

Results: While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-alpha or IFN-gamma exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally.

Conclusion: The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-gamma and TNF-alpha in protection following HK vaccination.

Show MeSH
Related in: MedlinePlus