Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.

[T gamma-delta lymphocytes and their role in hypersensitivity processes in the digestive and respiratory mucosa]. / Los linfocitos T gammadelta y su papel en procesos de hipersensibilidad en la mucosa digestiva y respiratoria.

Specific antigenic recognition by the immune system relies on receptors that T and B lymphocytes display on their plasmatic membranes. Most T cells express an antigen receptor integrated by an a chain and a b chain, the TcR-alphabeta. There is also a second population of T cells, minority in blood, spleen and lymph nodes, which expresses a different type of TcR, the TcR-gammadelta. These cells, termed gammadelta T cells, are probably implicated in the innate immunity, and are preferentially located in epithelia, where they are known as "gammadelta intraepithelial lymphocytes" (gammadelta IEL). The intestinal gammadelta IEL population (gammadelta i-IEL) is particularly abundant and it might have, at least in part, an extrathymic origin. An increase in the gammadelta i-IEL population has been described in intestinal hypersensitivity processes like Alimentary Allergy and, characteristically, Celiac Disease, but its significance is not well known. The second best known gammadelta IEL subset is the one located in the respiratory mucosa. Recent data suggest that these gammadelta IEL might play a role in protecting the normal airway function while being also implicated in allergic airway diseases, like Allergic Rhinitis and Asthma, due to their pro-inflammatory functions. This review focuses on the general characteristics of this yet poorly known and intriguing T cell population, whose relevance is increasingly acknowledged.

Los linfocitos T Gamma-Delta y su papel en procesos de hipersensibilidad en la mucosa digestiva y respiratoria

La mayoría de los linfocitos T, las células mejor conocidas del sistema inmune, expresan en su membrana un receptor para antígeno formado por una cadena Alfa y otra Beta, denominado TcR-Alfa Beta . Sin embargo, existe una segunda población de linfocitos T minoritaria en la sangre, bazo y ganglios linfáticos que presenta un TcR diferente, el TcR-Gamma Delta . Estos linfocitos, probablemente implicados en el sistema inmune innato, son sin embargo cuantitativamente importantes en los epitelios, donde se denominan "linfocitos intraepiteliales Gamma Delta" (LIE Gamma Delta). Los LIE Gamma Delta de la mucosa digestiva o i-LIE son especialmente abundantes y podrían tener, al menos en parte, un origen extratímico. Se ha descrito un aumento de la población i-LIE Gamma Delta en enfermedades intestinales como la alergia alimentaria o la enfermedad celíaca, aunque el significado de este aumento no es del todo conocido. La importancia los LIE Gamma Delta de la mucosa respiratoria es doble: por un lado, estarían encargados de la protección de la mucosa frente a agentes patógenos y, por otro, estarían implicados en procesos alérgicos como la rinitis alérgica crónica y el asma alérgica. En este trabajo se revisan las principales características de ésta, aún poco conocida pero interesante, estirpe linfoide, cuya relevancia está emergiendo gracias a los hallazgos que se han sucedido en los últimos años (AU)

Specific antigenic recognition by the immune system relies on receptors that T and B lymphocytes display on their plasmatic membranes. Most T cells express an antigen receptor integrated by an a chain and a b chain, the TcR-αβ. There is also a second population of T cells, minoritary in blood, spleen and lymph nodes, which expresses a different type of TcR, the TcR-γδ. These cells, termed γδ T cells, are probably implicated in the innate immunity, and are preferentially located in epithelia, where they are known as "γδ intraepithelial lymphocytes" (γδ IEL). The intestinal γδ IEL population (γδ i-IEL) is particularly abundant and it might have, at least in part, an extrathymic origin. An increase in the γδ i-IEL population has been described in intestinal hypersensitivity processes like Alimentary Allergy and, characteristically, Celiac Disease, but its significance is not well known. The second best known γδ IEL subset is the one located in the respiratory mucosa. Recent data suggest that these γδ IEL might play a role in protecting the normal airway fuction while being also implicated in allergic airway diseases, like Allergic Rhinitis and Asthma, due to their pro-inflammatory functions. This review focuses on the general caracteristics of this yet poorly known and intriguing T cell population, whose relevance is increasingly acknowledged (AU)