title: Hsp65-ProducingLactococcus lactisPrevents Inflammatory Intestinal Disease in Mice by IL-10- and TLR2-Dependent Pathways.
abstract: Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria. Using an IBD mouse model, we showed that oral pretreatment with genetically modifiedLactococcus lactisthat produces and releasesMycobacteriumHsp65, completely prevented DSS-induced colitis in C57BL/6 mice. Protection was associated with reduced pro-inflammatory cytokines, such as IFN-γ, IL-6, and TNF-α; increased IL-10 production in colonic tissue; and expansion of CD4+Foxp3+and CD4+LAP+regulatory T cells in spleen and mesenteric lymph nodes. This effect was dependent on IL-10 and toll-like receptor 2. Thus, this approach may open alternative options for long-term management of IBD.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Centro Universitário UNA, Belo Horizonte, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Gomes-Santos
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Instituto Federal do Paraná, Palmas, Brazil.
authors.forename: Rafael Pires
authors.initials: RP
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Thaís Garcias
authors.initials: TG
authors.lastname: Moreira
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Archimedes Barbosa
authors.initials: AB
authors.lastname: Castro-Junior
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Bernardo Coelho
authors.initials: BC
authors.lastname: Horta
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Luísa
authors.initials: L
authors.lastname: Lemos
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Departamento de Microbiologia e Imunologia, Universidade Federal de Alfenas, Alfenas, Brazil.
authors.forename: Leonardo Augusto
authors.initials: LA
authors.lastname: de Almeida
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Ann Ronmey Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rafael Machado
authors.initials: RM
authors.lastname: Rezende
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Denise Carmona
authors.initials: DC
authors.lastname: Cara
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Sérgio Costa
authors.initials: SC
authors.lastname: Oliveira
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Vasco Ariston Carvalho
authors.initials: VA
authors.lastname: Azevedo
authors.affiliation: Departamento de Biologia Geral, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Ana Maria Caetano
authors.initials: AM
authors.lastname: Faria
keywords: DSS; Hsp; IL-10; Lactococcus lactis; TLR2; colitis