title: BCG infection in mice is promoted by naïve mesenchymal stromal cells (MSC) and suppressed by poly(A:U)-conditioned MSC.
abstract: Mesenchymal stromal cells (MSC) transplantation is an actively studied therapeutic approach used in regenerative medicine and in the field of control of immunoinflammatory response. Conditioning of MSC in culture can form their predominantly pro- or anti-inflammatory phenotypes. We demonstrated that poly(A:U)-conditioning of bone marrow-derived mouse MSC induced predominantly pro-inflammatory phenotype. The effects of administration of naïve MSC (nMSC) or conditioned MSC (cMSC) on the course of mycobacterial infection were studied. BALB/c mice infected i.p. with 5 × 106M. bovis BCG were successively injected i.v. with 0.75 × 106of nMSC or cMSC in 11 and 12.5 weeks after infection and sacrificed at the week 14. Histological and bacteriological examination of BCG-infected animals revealed low bacterial loads in liver, lungs and spleen; the bacterial load in spleen was higher than in other organs. Treatment with nMSC induced 3-fold increase of the number of bacteria in spleen granulomas, while cMSC decreased significantly the number of bacteria in BCG-positive granulomas. Analysis of preparations of organ homogenates by luminescent microscopy, MGIT cultures and CFU count on Lowenstein-Jensen medium revealed that nMSC promoted mycobacterial growth whereas cMSC suppressed mycobacterial growth significantly. We concluded that MSC therapy can be effective in mycobacterial infection, but only in a case of appropriate conditioning of the cells.
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia; Research Institute for Internal and Preventive Medicine, Borisa Bogatkova 175/1, Novosibirsk, 630089, Russia. Electronic address: YShSchwartz@mail.ru.
authors.forename: Yakov Sh
authors.initials: YS
authors.lastname: Schwartz
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia; Research Institute for Fundamental and Clinical Immunology, Krasny Prospekt 42a, Novosibirsk, 630099, Russia. Electronic address: S.Belogorodtsev@mail.ru.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Belogorodtsev
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia. Electronic address: pfilimonov@yandex.ru.
authors.forename: Pavel N
authors.initials: PN
authors.lastname: Filimonov
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia. Electronic address: bact.nniit@gmail.com.
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Cherednichenko
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia. Electronic address: sergey.pustylnikov@gmail.com.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Pustylnikov
authors.affiliation: Novosibirsk Tuberculosis Research Institute, Okhotskaya 81a, Novosibirsk, 630040, Russia. Electronic address: nniit@sibnet.ru.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Krasnov
mesh_terms: D000818:Animals; D058491:Bacterial Load; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D054884:Host-Pathogen Interactions / Q000276:immunology; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000254:growth & development* / Q000302:isolation & purification; D011131:Polyribonucleotides / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D011131:Polyribonucleotides; C044366:poludan
keywords: BCG; Cell therapy; Granuloma; Mesenchymal stromal cells; Tuberculosis