4.6 Article

Mechanisms of group B streptococcal-induced apoptosis of murine macrophages

Journal

JOURNAL OF IMMUNOLOGY
Volume 175, Issue 4, Pages 2555-2562

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.4.2555

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Funding

  1. NCI NIH HHS [R01 CA76379] Funding Source: Medline
  2. NIAID NIH HHS [R01 AI40918] Funding Source: Medline
  3. PHS HHS [21765] Funding Source: Medline

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Apoptosis of murine and human macrophages induced by group B Streptococcus agalactiae (GBS) is likely an important virulence mechanism that is used by the bacteria to suppress the host immune response and to persist at sites of infection. The mechanisms by which GBS induces apoptosis are, however, largely unknown. In this study, we report that in murine macrophages GBS induces unique changes in the regulation and localization of the apoptotic regulators Bad, 14-3-3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome c and the activation of caspase-9 and caspase-3. Furthermore, inhibition of caspase-3 impaired GBS-induced apoptosis of macrophages. The ability to modulate the activity of effector caspases may therefore represent an unexploited avenue for therapeutic intervention in GBS infections.

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