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Additionally, internalized<jats:italic>Y. pestis<\/jats:italic>can survive in the phagosomes of nai\u0308ve or gamma interferon (IFN-\u03b3)-activated macrophages by blocking vacuole acidification. The<jats:italic>Y. pestis<\/jats:italic>LcrV protein is a target of protective antibodies. The binding of antibodies to LcrV at the injectisome tip results in neutralization of the apoptosis of<jats:italic>Y. pestis<\/jats:italic>-infected macrophages and is used as an in vitro correlate of protective immunity. The cytokines IFN-\u03b3 and tumor necrosis factor alpha can cooperate with anti-LcrV to promote protection against lethal<jats:italic>Y. pestis<\/jats:italic>infection in mice. It is not known if these phagocyte-activating cytokines cooperate with anti-LcrV to increase the killing of the pathogen and decrease apoptosis in macrophages. We investigated how anti-LcrV and IFN-\u03b3 impact bacterial survival and apoptosis in cultured murine macrophages infected with<jats:italic>Y. pestis<\/jats:italic>KIM5.<jats:italic>Y. pestis<\/jats:italic>KIM5 opsonized with polyclonal or monoclonal anti-LcrV was used to infect macrophages treated with or without IFN-\u03b3. The phagocytosis and survival of KIM5 and the apoptosis of macrophages were measured at different time points postinfection. The results show that anti-LcrV reduced apoptosis at an early time point (5 h) but not at a later time point (24 h). Polyclonal anti-LcrV was unable to inhibit apoptosis at either time point in IFN-\u03b3-activated macrophages. Additionally, anti-LcrV was ineffective at promoting the killing of KIM5 in nai\u0308ve or activated macrophages. We conclude that<jats:italic>Y. pestis<\/jats:italic>can bypass protective antibodies to LcrV and activation with IFN-\u03b3 to survive and induce apoptosis in murine macrophages.<\/jats:p>","DOI":"10.1128\/cvi.00172-09","type":"journal-article","created":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T02:00:27Z","timestamp":1251338427000},"page":"1457-1466","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["<i>Yersinia pestis<\/i>Can Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages"],"prefix":"10.1128","volume":"16","author":[{"given":"Betty L.","family":"Noel","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarit","family":"Lilo","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Capurso","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Hill","sequence":"additional","affiliation":[{"name":"Directorate Strategic Technologies, 1-L-20, MOD Main Building, Whitehall, London SWAB 2HB, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Bliska","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"14043","DOI":"10.1073\/pnas.96.24.14043","volume":"96","year":"1999","unstructured":"Achtman, M., K. 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