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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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TNF-α impact on chronic B. mallei infection. BALB/c mice challenged i.p. with 1 × 106 CFU B. mallei were depleted of TNF-α (n = 6) or antibody control (n = 5) at day 42 post infection. Rapid mortality was observed at 7 days post TNF-α depletion (p = 0.0023).
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Figure 5: TNF-α impact on chronic B. mallei infection. BALB/c mice challenged i.p. with 1 × 106 CFU B. mallei were depleted of TNF-α (n = 6) or antibody control (n = 5) at day 42 post infection. Rapid mortality was observed at 7 days post TNF-α depletion (p = 0.0023).

Mentions: Similar studies were performed to determine the role of IFN-γ or TNF-α in acute infection in BALB/c mice immunized with HK bacteria. Six hours before challenge, mice were dosed with antibodies that neutralize IFN-γ or TNF-α. Individual depletion of either TNF-α (p = 0.0145) or IFN-γ (p = 0.0446) resulted in 100% mortality with an MST of 3 and 2 days, respectively, compared to the HK-vaccinated isotype control mice (Fig. 4). In contrast, 40% of HK-vaccinated, isotype control mice survived to at least 12 days post-challenge (Fig 4). To further evaluate the host TNF-α response during an established B. mallei chronic infection, we infected 12 BALB/c mice by the i.p. route with 1 × 106 CFU B. mallei. One animal was terminally ill on day 37 post-infection. On day 42 post-infection, the remaining 11 mice were dosed with either anti-TNF-α (n = 6), or control mAb (AFRC Mac 49) (n = 5). No further deaths were observed in the control mAb-treated mice. Rapid mortality was observed in the anti-TNF-α-treated group, with all mice dying within 7 days of treatment (p = 0.0023) relative to the isotype-treated controls (Fig. 5).


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)

TNF-α impact on chronic B. mallei infection. BALB/c mice challenged i.p. with 1 × 106 CFU B. mallei were depleted of TNF-α (n = 6) or antibody control (n = 5) at day 42 post infection. Rapid mortality was observed at 7 days post TNF-α depletion (p = 0.0023).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: TNF-α impact on chronic B. mallei infection. BALB/c mice challenged i.p. with 1 × 106 CFU B. mallei were depleted of TNF-α (n = 6) or antibody control (n = 5) at day 42 post infection. Rapid mortality was observed at 7 days post TNF-α depletion (p = 0.0023).
Mentions: Similar studies were performed to determine the role of IFN-γ or TNF-α in acute infection in BALB/c mice immunized with HK bacteria. Six hours before challenge, mice were dosed with antibodies that neutralize IFN-γ or TNF-α. Individual depletion of either TNF-α (p = 0.0145) or IFN-γ (p = 0.0446) resulted in 100% mortality with an MST of 3 and 2 days, respectively, compared to the HK-vaccinated isotype control mice (Fig. 4). In contrast, 40% of HK-vaccinated, isotype control mice survived to at least 12 days post-challenge (Fig 4). To further evaluate the host TNF-α response during an established B. mallei chronic infection, we infected 12 BALB/c mice by the i.p. route with 1 × 106 CFU B. mallei. One animal was terminally ill on day 37 post-infection. On day 42 post-infection, the remaining 11 mice were dosed with either anti-TNF-α (n = 6), or control mAb (AFRC Mac 49) (n = 5). No further deaths were observed in the control mAb-treated mice. Rapid mortality was observed in the anti-TNF-α-treated group, with all mice dying within 7 days of treatment (p = 0.0023) relative to the isotype-treated controls (Fig. 5).

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