RESUMEN
How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
Asunto(s)
Inmunidad Adaptativa , Inmunidad Innata , Linfocitos/inmunología , Micronutrientes/deficiencia , Deficiencia de Vitamina A/inmunología , Vitamina A/inmunología , Animales , Citrobacter rodentium/inmunología , Infecciones por Enterobacteriaceae/inmunología , Proteínas de Homeodominio/genética , Interleucina-13/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones MutantesRESUMEN
The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T(reg) cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes.
Asunto(s)
Colitis/inmunología , ADN Bacteriano/inmunología , Inmunidad Mucosa/efectos de los fármacos , Mucosa Intestinal/inmunología , Motivos de Nucleótidos , Oligodesoxirribonucleótidos/inmunología , Animales , Antibacterianos/farmacología , Colitis/inducido químicamente , Colitis/microbiología , Islas de CpG/inmunología , Citocinas/biosíntesis , Citocinas/inmunología , ADN Bacteriano/química , ADN Bacteriano/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Encephalitozoon cuniculi/efectos de los fármacos , Encephalitozoon cuniculi/inmunología , Escherichia coli/inmunología , Factores Inmunológicos/química , Factores Inmunológicos/genética , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Lactobacillus/inmunología , Ratones , Ratones Transgénicos , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/farmacología , Probióticos/farmacología , Dodecil Sulfato de Sodio , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Toxoplasma/efectos de los fármacos , Toxoplasma/inmunologíaAsunto(s)
Alcaloides de Amaryllidaceae , Antineoplásicos/farmacología , Alcaloides de Belladona/farmacología , Encephalitozoon/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Fenantridinas/farmacología , Animales , Línea Celular , Encephalitozoon/crecimiento & desarrollo , Encephalitozoon/ultraestructura , Concentración 50 Inhibidora , Microscopía Electrónica , Pruebas de Sensibilidad Parasitaria , Conejos , Ribosa/química , Estaurosporina/químicaRESUMEN
Microsporidia are unicellular and obligate intracellular spore-forming parasites. The spore inoculates the host cell with its non-motile infectious content, the sporoplasm, by way of the polar tube--the typical invasive apparatus of the microsporidian spore. Molecules involved in host cell invasion were investigated in Encephalitozoon intestinalis. Mouse polyclonal and monoclonal antibodies were raised against spore proteins and their reactivity was tested by Western-blotting and immunolocalization techniques, including electron and confocal microscopy. The antibodies thus generated could be divided into two major groups. One group reacted to the surface of the parasite at different developmental stages, mostly presporous stages and mature spores, whereas the other group recognized the polar tube. Of the antibodies reacting to the spore wall, one identified an exospore protein at 125 kDa while all others recognized a major doublet at 55-60 kDa, and minor proteins present at the surface of sporogonic stages and in the endospore. All antibodies recognizing spore wall proteins reacted also to the material forming septa in the parasitophorous vacuole. A major polar tube protein at 60 kDa was identified by another group of antibodies.