| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208
The role of Abs in protection against respiratory infection with the intracellular bacterium Francisella tularensis is not clear. To investigate the ability of Abs to clear bacteria from the lungs and prevent systemic spread, immune serum was passively administered i.p. to naive mice before intranasal F. tularensis live vaccine strain infection. It was found that immune serum treatment provided 100% protection against lethal challenge while normal serum or Ig-depleted immune serum provided no protection. Protective efficacy was correlated with increased clearance of bacteria from the lung and required expression of Fc
R on phagocytes, including macrophages and neutrophils. However, complement was not required for protection. In vitro experiments demonstrated that macrophages were more readily infected by Ab-opsonized bacteria but became highly efficient in killing upon activation by IFN-. Consistent with this finding, in vivo Ab-mediated protection was found to be dependent upon IFN-. SCID mice were not protected by passive Ab transfer, suggesting that T cells but not NK cells serve as the primary source for IFN-. These data suggest that a critical interaction of humoral and cellular immune responses is necessary to provide sterilizing immunity against F. tularensis. Of considerable interest was the finding that serum Abs were capable of conferring protection against lethal respiratory tularemia when given 24–48 h postexposure. Thus, this study provides the first evidence for the therapeutic use of Abs in Francisella-infected individuals.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant PO1 AI056320 (to D.W.M.) and Career Development Award U54 AI057158 from the Northeast Regional Center of Excellence in Biodefense and Emerging Infections (to G.S.K.).
2 Address correspondence and reprint requests to Dr. Dennis W. Metzger, Center for Immunology and Microbial Disease, Albany Medical College, MC-151, 47 New Scotland Avenue, Albany, NY 12208. E-mail address: metzged{at}mail.amc.edu
3 Abbreviations used in this paper: i.d., intradermal; LVS, live vaccine strain; i.n., intranasal; MOI, multiplicity of infection.
This article has been cited by other articles:
|
|
 |
|
  J. E. Wilson, B. Katkere, and J. R. Drake Francisella tularensis Induces Ubiquitin-Dependent Major Histocompatibility Complex Class II Degradation in Activated Macrophages Infect. Immun., November 1, 2009; 77(11): 4953 - 4965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Crane, S. L. Warner, and C. M. Bosio A Novel Role for Plasmin-Mediated Degradation of Opsonizing Antibody in the Evasion of Host Immunity by Virulent, but Not Attenuated, Francisella tularensis J. Immunol., October 1, 2009; 183(7): 4593 - 4600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mahawar, G. S. Kirimanjeswara, D. W. Metzger, and C. S. Bakshi Contribution of Citrulline Ureidase to Francisella tularensis Strain Schu S4 Pathogenesis J. Bacteriol., August 1, 2009; 191(15): 4798 - 4806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bitsaktsis, D. B. Rawool, Y. Li, N. V. Kurkure, B. Iglesias, and E. J. Gosselin Differential Requirements for Protection against Mucosal Challenge with Francisella tularensis in the Presence versus Absence of Cholera Toxin B and Inactivated F. tularensis J. Immunol., April 15, 2009; 182(8): 4899 - 4909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Ray, Y. Cong, A. K. Murthy, D. M. Selby, K. E. Klose, J. R. Barker, M. N. Guentzel, and B. P. Arulanandam Oral Live Vaccine Strain-Induced Protective Immunity against Pulmonary Francisella tularensis Challenge Is Mediated by CD4+ T Cells and Antibodies, Including Immunoglobulin A Clin. Vaccine Immunol., April 1, 2009; 16(4): 444 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Savitt, P. Mena-Taboada, G. Monsalve, and J. L. Benach Francisella tularensis Infection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy Clin. Vaccine Immunol., March 1, 2009; 16(3): 414 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Qin, D. W. Scott, J. A. Thompson, and B. J. Mann Identification of an Essential Francisella tularensis subsp. tularensis Virulence Factor Infect. Immun., January 1, 2009; 77(1): 152 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. O. Hazlett, S. D. Caldon, D. G. McArthur, K. A. Cirillo, G. S. Kirimanjeswara, M. L. Magguilli, M. Malik, A. Shah, S. Broderick, I. Golovliov, et al. Adaptation of Francisella tularensis to the Mammalian Environment Is Governed by Cues Which Can Be Mimicked In Vitro Infect. Immun., October 1, 2008; 76(10): 4479 - 4488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Huntley, P. G. Conley, D. A. Rasko, K. E. Hagman, M. A. Apicella, and M. V. Norgard Native Outer Membrane Proteins Protect Mice against Pulmonary Challenge with Virulent Type A Francisella tularensis Infect. Immun., August 1, 2008; 76(8): 3664 - 3671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ben Nasr and G. R. Klimpel Subversion of complement activation at the bacterial surface promotes serum resistance and opsonophagocytosis of Francisella tularensis J. Leukoc. Biol., July 1, 2008; 84(1): 77 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Qin, D. W. Scott, and B. J. Mann Francisella tularensis subsp. tularensis Schu S4 Disulfide Bond Formation Protein B, but Not an RND-Type Efflux Pump, Is Required for Virulence Infect. Immun., July 1, 2008; 76(7): 3086 - 3092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Rawool, C. Bitsaktsis, Y. Li, D. R. Gosselin, Y. Lin, N. V. Kurkure, D. W. Metzger, and E. J. Gosselin Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis J. Immunol., April 15, 2008; 180(8): 5548 - 5557. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
