Effects of live and inactivated VSL#3 probiotic preparations in the modulation of in vitro and in vivo allergen-induced Th2 responses.
BACKGROUND
The immunological mechanisms responsible for the immunomodulatory and anti-allergic effects of probiotic bacteria are still poorly defined. The combined effects of mixtures of different species of probiotic bacteria have been explored only in part. The present study describes the immunomodulatory activity of the VSL#3 probiotic preparation in in vitro and in vivo systems.


METHODS
The activation and cytokine production by in vitro probiotic-stimulated bone-marrow dendritic cells (BM-DCs) and spleen cells isolated from naïve or Par j 1-sensitized mice were investigated. Mice were intranasally administered a sonicate preparation of VSL#3 before immunization with rPar j 1. Serum antibody levels and cytokine expression in the lung were determined.


RESULTS
Both live and sonicated VSL#3 preparations induced maturation and cytokine production by BM-DCs. Cytokine production by spleen cells from naïve or Par j 1-sensitized mice was modulated by the probiotic preparations towards a Treg/Th0 profile, characterized by increased IL-10 and IFN-gamma production. In vivo prophylactic treatment with VSL#3 induced a significant reduction of serum specific IgG1. At lung level, VSL#3 pre-treatment remarkably reduced IL-13 and IL-4 mRNA expression and increased IL-10 expression.


CONCLUSIONS
The VSL#3 preparations have not only the capacity to bias primary immune responses towards a Treg/Th0-type profile, but also to modify in the same way the functional characteristics of established in vitro Th2 responses. In vivo studies on a mouse model of Par j 1 sensitization indicate that the prophylactic intranasal treatment with probiotic bacteria is able to modulate the development of Th2-biased responses.
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Giorgia
G
Mastrangeli
Silvia
S
Corinti
Cinzia
C
Butteroni
Claudia
C
Afferni
Angela
A
Bonura
Monica
M
Boirivant
Paolo
P
Colombo
Gabriella
G
Di Felice
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000276:immunology; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D020825:T-Box Domain Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D000098815:T-bet Transcription Factor
D000485:Allergens; D015703:Antigens, CD; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007136:Immunoglobulins; D018793:Interleukin-13; D015848:Interleukin-5; D008070:Lipopolysaccharides; C083860:Par j I protein, Parietaria judaica; D010940:Plant Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma