RESUMEN
The intestinal microbiome may have a critical roll in susceptibility or resistance to immune-mediated diseases. Alterations of the gut microflora after oral antibiotic treatment can regulate encephalomyelitis (EAE), an animal model for human multiple sclerosis (MS). We now show that a zwitterionic capsular polysaccharide A (PSA) of Bacteroides fragilis can protect against central nervous system demyelinating disease. Oral administration with purified PSA protected mice against EAE prophylactic and therapeutically. PSA treatment enhanced CD103 expressing dendritic cells (DCs) that accumulated in the cervical lymph nodes. Exposure of naïve DCs to PSA induced the conversion of naïve CD4(+) T cells into interleukin (IL)-10-producing FoxP3(+)Treg cells. Protection against EAE was completely abrogated in IL-10-deficient mice. Our results show an important role for a molecule from human commensal bacteria in protecting against EAE and suggest the possibility for protection in MS.
Asunto(s)
Bacteroides fragilis/inmunología , Células Dendríticas/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/inmunología , Esclerosis Múltiple/inmunología , Polisacáridos Bacterianos/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Administración Oral , Animales , Antígenos CD/biosíntesis , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/microbiología , Encefalomielitis Autoinmune Experimental/prevención & control , Humanos , Cadenas alfa de Integrinas/biosíntesis , Interleucina-10/biosíntesis , Interleucina-10/genética , Interleucina-10/metabolismo , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Esclerosis Múltiple/tratamiento farmacológico , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
We tested the immunogenicity in mice of a recombinant fusion protein (gp41HA) consisting of the ectodomain of the HIV-1(IIIB) envelope glycoprotein gp41 fused to a fragment of the influenza virus HA2 hemagglutinin protein. An intraperitoneal prime followed by intranasal or intragastric boosts with gp41HA induced high concentrations of serum IgG antibodies and fecal IgA antibodies that reacted with gp41 in HIV-1(IIIB) viral lysate and were cross-reactive with gp41 in HIV-1(MN) lysate. By indirect immunofluorescence, serum IgG and fecal IgA from immunized mice were also shown to recognize gp41 in acetone-fixed human peripheral blood mononuclear cells infected with either syncytium-inducing (SI) or non-syncytium-inducing (NSI) North American HIV-1 field isolates, but not uninfected cells. Thus, this recombinant antigen may be useful in prime/boost immunization protocols designed to induce systemic and mucosal antibodies that recognize multiple primary HIV-1 isolates.
