title: Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein.
abstract: We have previously reported that mice immunized with the mycobacterial 27-kDa lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge. We also showed that 27-kDa lipoprotein abrogated the protection afforded by the BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein may modulate the course of experimental mycobacterial infection. In this study, we address the role of the 27-kDa lipoprotein in modulating the immune response to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa-infected mice compared to Mtb-infected mice. Furthermore, during infection, splenocytes and purified T cells lost their ability to proliferate in response to concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was accompanied by high IFN-gamma and NO production, but low TNF-alpha secretion levels. Addition of L-NMMA, anti-IFN-gamma and anti-TNF-alpha antibodies restored in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short-term L-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated immunosuppression and increase in susceptibility to Mtb. Altogether, these data suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing increased suppression of the immune response due to elevated NO production.
authors.affiliation: Department of Clinical Microbiology, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Avi-Hai
authors.initials: AH
authors.lastname: Hovav
authors.forename: Jacob
authors.initials: J
authors.lastname: Mullerad
authors.forename: Alexander
authors.initials: A
authors.lastname: Maly
authors.forename: Liuba
authors.initials: L
authors.lastname: Davidovitch
authors.forename: Yolanta
authors.initials: Y
authors.lastname: Fishman
authors.forename: Herve
authors.initials: H
authors.lastname: Bercovier
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D008074:Lipoproteins / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000382:microbiology; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D008074:Lipoproteins; C110121:P27 protein, Mycobacterium; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma