| Autor: |
CoIe, Leah E., Yang Yang, Elkins, Karen L., Fernandez, Ellen T., Qureshi, Nilofer, Shlomchik, Mark J., Herzenberg, Leonard A., Herzenberg, Leonore A., Vogel, Stefanie N. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/17/2009, Vol. 106 Issue 11, p4343-4348, 6p, 3 Graphs |
| Abstrakt: |
Francisella tularensis (Ft), a Gram-negative intracellular bacterium. is the etiologic agent of tularemia. Infection of mice with <10 Ft Live Vaccine Strain (Ft LVS) organisms i.p. causes a lethal infection that resembles human tularemia. Here, we show that immunization with as little as 0.1 ng Ft LVS lipopolysaccharide (Ft-LPS), but not Ft lipid A, generates a rapid antibody response that protects wild-type (WT) mice against lethal Ft LVS challenge. Protection is not induced in Ft-LPS-immunized B cell-deficient mice (μMT or JhD), male xid mice, or Ig transgenic mice that produce a single IgH (not reactive with Ft-LPS). Focusing on the cellular mechanisms that underlie this protective response, we show that Ft-LPS specifically stimulates proliferation of B-la lymphocytes that bind fluorochrOme-labeled Ft-LPS and the differentiation of these cells to plasma cells that secrete antibodies specific for Ft-LPS. This exclusively B-la antibody response is equivalent in WT, T-deficient (TCRαβ[sup-/-], TCRγδ[sup-/-]), and Toll-like receptor 4 (TLR4)-deficient (TLR4[sup-/-]) mice and thus is not dependent on T cells or typical inflammatory processes. Serum antibody levels peak ≈5 days after Ft-LPS immunization and persist at low levels for months. Thus, immunization with Ft-LPS activates a rare population of antigenspecific B-la cells to produce a persistent T-independent antibody response that provides long-term protection against lethal Ft LVS infection. These data support the possibility of creating effective, minimally invasive vaccines that can provide effective protection against pathogen invasion. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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