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Infection and Immunity, June 2004, p. 3383-3390, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3383-3390.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mitogenicity of the Recombinant Mycobacterial 27-Kilodalton Lipoprotein Is Not Connected to Its Antiprotective Effect

Avi-Hai Hovav,¹ Liuba Davidovitch,¹ Gabriel Nussbaum,² Jacob Mullerad,³ Yolanta Fishman,¹ and Herve Bercovier^1*

Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University,¹ Department of Oral Biology, The Hebrew University—Hadassah School of Dental Medicine, Jerusalem,² Department of Clinical Biochemistry, Rambam Medical Center, Haifa, Israel³

Received 15 December 2003/ Returned for modification 16 January 2004/ Accepted 27 February 2004

We reported previously that even though immunization with the recombinant mycobacterial 27-kDa lipoprotein (r27) induced a Th1-type response in mice, the vaccinated mice became more susceptible to challenge with Mycobacterium tuberculosis. In this study we show that r27 stimulates naive splenocytes to proliferate. Acylation of r27 was crucial for this effect, since a nonacylated mutant of r27, termed r27SP, failed to stimulate splenocytes either in vitro or in vivo. Depletion experiments indicated that only B cells were proliferating in a T-cell-independent manner. We also found that r27 is recognized by TLR2, which is involved in mitogenic stimulation. Interestingly, r27 but not r27SP induced high gamma interferon levels in splenocyte supernatants, whereas no significant interleukin-2 levels were detected. Since B-cell polyclonal activation might aggravate pathogen infection, we asked whether the antiprotective effect of the r27 lipoprotein is associated with its mitogenicity. We showed that, as in the case of r27, immunization of mice with the nonmitogenic r27SP lipoprotein resulted in increased M. tuberculosis multiplication. We conclude that the antiprotective effect of the r27 lipoprotein must be linked to properties of the polypeptide portion of the lipoprotein rather than to its lipid moiety and its mitogenicity.

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* Corresponding author. Mailing address: Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, P.O. Box 12272, Jerusalem, Israel. Phone: 972-2-6758256. Fax: 972-2-6784010. E-mail: hb{at}cc.huji.ac.il.

Editor: S. H. E. Kaufmann

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Infection and Immunity, June 2004, p. 3383-3390, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3383-3390.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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