Mitogenicity of the recombinant mycobacterial 27-kilodalton lipoprotein is not connected to its antiprotective effect.
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 r27DeltaSP, 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 r27DeltaSP 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 r27DeltaSP 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.
Hovav
Avi-Hai
AH
Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Davidovitch
Liuba
L
Nussbaum
Gabriel
G
Mullerad
Jacob
J
Fishman
Yolanta
Y
Bercovier
Herve
H
D000215:Acylation; D000818:Animals; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D006801:Humans; D007114:Immunization; D008074:Lipoproteins / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000942:Antigens, Bacterial; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D032581:Tuberculosis Vaccines