Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
Annu Rev Immunol ; 36: 359-381, 2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29400985

RESUMO

IgA is the dominant immunoglobulin isotype produced in mammals, largely secreted across the intestinal mucosal surface. Although induction of IgA has been a hallmark feature of microbiota colonization following colonization in germ-free animals, until recently appreciation of the function of IgA in host-microbial mutualism has depended mainly on indirect evidence of alterations in microbiota composition or penetration of microbes in the absence of somatic mutations in IgA (or compensatory IgM). Highly parallel sequencing techniques that enable high-resolution analysis of either microbial consortia or IgA sequence diversity are now giving us new perspectives on selective targeting of microbial taxa and the trajectory of IgA diversification according to induction mechanisms, between different individuals and over time. The prospects are to link the range of diversified IgA clonotypes to specific antigenic functions in modulating the microbiota composition, position and metabolism to ensure host mutualism.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunoglobulina A/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Fatores Etários , Animais , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mucosa Intestinal/metabolismo , Ligação Proteica
2.
Nature ; 584(7820): 274-278, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760003

RESUMO

Colonization by the microbiota causes a marked stimulation of B cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires1,2. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice3 to deconstruct how the microbiota shapes the B cell pool and its functional responsiveness. We followed the development of the immunoglobulin repertoire in B cell populations, as well as single cells by deep sequencing. Microbial exposures at the intestinal mucosa generated oligoclonal responses that differed from those of germ-free mice, and from the diverse repertoire that was generated after intravenous systemic exposure to microbiota. The IgA repertoire-predominantly to cell-surface antigens-did not expand after dose escalation, whereas increased systemic exposure broadened the IgG repertoire to both microbial cytoplasmic and cell-surface antigens. These microbial exposures induced characteristic immunoglobulin heavy-chain repertoires in B cells, mainly at memory and plasma cell stages. Whereas sequential systemic exposure to different microbial taxa diversified the IgG repertoire and facilitated alternative specific responses, sequential mucosal exposure produced limited overlapping repertoires and the attrition of initial IgA binding specificities. This shows a contrast between a flexible response to systemic exposure with the need to avoid fatal sepsis, and a restricted response to mucosal exposure that reflects the generic nature of host-microbial mutualism in the mucosa.


Assuntos
Linfócitos B/citologia , Linfócitos B/imunologia , Imunidade nas Mucosas/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Simbiose/imunologia , Administração Intravenosa , Administração Oral , Animais , Clostridiales/imunologia , Clostridiales/isolamento & purificação , Escherichia coli/imunologia , Escherichia coli/isolamento & purificação , Feminino , Vida Livre de Germes , Imunoglobulina A/química , Imunoglobulina A/imunologia , Imunoglobulina G/química , Imunoglobulina G/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Memória Imunológica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmócitos/citologia , Plasmócitos/imunologia , Priming de Repetição
4.
Cell Host Microbe ; 29(4): 650-663.e9, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33662276

RESUMO

Isobiotic mice, with an identical stable microbiota composition, potentially allow models of host-microbial mutualism to be studied over time and between different laboratories. To understand microbiota evolution in these models, we carried out a 6-year experiment in mice colonized with 12 representative taxa. Increased non-synonymous to synonymous mutation rates indicate positive selection in multiple taxa, particularly for genes annotated for nutrient acquisition or replication. Microbial sub-strains that evolved within a single taxon can stably coexist, consistent with niche partitioning of ecotypes in the complex intestinal environment. Dietary shifts trigger rapid transcriptional adaptation to macronutrient and micronutrient changes in individual taxa and alterations in taxa biomass. The proportions of different sub-strains are also rapidly altered after dietary shift. This indicates that microbial taxa within a mouse colony adapt to changes in the intestinal environment by long-term genomic positive selection and short-term effects of transcriptional reprogramming and adjustments in sub-strain proportions.


Assuntos
Adaptação Fisiológica , Microbioma Gastrointestinal/fisiologia , Microbiota/fisiologia , Adaptação Fisiológica/imunologia , Animais , Bactérias/genética , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Genômica , Imunidade , Intestinos , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Ralstonia , Simbiose
5.
Nat Commun ; 11(1): 1978, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332737

RESUMO

There is the notion that infection with a virulent intestinal pathogen induces generally stronger mucosal adaptive immunity than the exposure to an avirulent strain. Whether the associated mucosal inflammation is important or redundant for effective induction of immunity is, however, still unclear. Here we use a model of auxotrophic Salmonella infection in germ-free mice to show that live bacterial virulence factor-driven immunogenicity can be uncoupled from inflammatory pathogenicity. Although live auxotrophic Salmonella no longer causes inflammation, its mucosal virulence factors remain the main drivers of protective mucosal immunity; virulence factor-deficient, like killed, bacteria show reduced efficacy. Assessing the involvement of innate pathogen sensing mechanisms, we show MYD88/TRIF, Caspase-1/Caspase-11 inflammasome, and NOD1/NOD2 nodosome signaling to be individually redundant. In colonized animals we show that microbiota metabolite cross-feeding may recover intestinal luminal colonization but not pathogenicity. Consequent immunoglobulin A immunity and microbial niche competition synergistically protect against Salmonella wild-type infection.


Assuntos
Imunidade nas Mucosas , Mucosa Intestinal/microbiologia , Infecções por Salmonella/microbiologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Antígenos de Bactérias , Caspase 1/metabolismo , Caspases Iniciadoras/metabolismo , Proliferação de Células , Microbioma Gastrointestinal , Imunidade Inata , Imunoglobulina A/imunologia , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Fator 88 de Diferenciação Mieloide/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Salmonella typhimurium/patogenicidade , Transdução de Sinais , Virulência , Fatores de Virulência
6.
Science ; 363(6430): 993-998, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819965

RESUMO

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.


Assuntos
Estresse do Retículo Endoplasmático , Células Epiteliais/imunologia , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Mucosa Intestinal/imunologia , Animais , Autofagia , Proteínas Relacionadas à Autofagia/genética , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Plasmócitos/imunologia , Técnicas de Cultura de Tecidos , Proteína 1 de Ligação a X-Box/genética
7.
Genome Announc ; 4(5)2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27634994

RESUMO

We report here the complete genome sequences of 12 bacterial species of stable defined moderately diverse mouse microbiota 2 (sDMDMm2) used to colonize germ-free mice with defined microbes. Whole-genome sequencing of these species was performed using the PacBio sequencing platform yielding circularized genome sequences of all 12 species.

9.
Nat Commun ; 6: 8292, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26392213

RESUMO

The overall composition of the mammalian intestinal microbiota varies between individuals: within each individual there are differences along the length of the intestinal tract related to host nutrition, intestinal motility and secretions. Mucus is a highly regenerative protective lubricant glycoprotein sheet secreted by host intestinal goblet cells; the inner mucus layer is nearly sterile. Here we show that the outer mucus of the large intestine forms a unique microbial niche with distinct communities, including bacteria without specialized mucolytic capability. Bacterial species present in the mucus show differential proliferation and resource utilization compared with the same species in the intestinal lumen, with high recovery of bioavailable iron and consumption of epithelial-derived carbon sources according to their genome-encoded metabolic repertoire. Functional competition for existence in this intimate layer is likely to be a major determinant of microbiota composition and microbial molecular exchange with the host.


Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Mucosa Intestinal/microbiologia , Animais , Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Vida Livre de Germes , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Família Multigênica , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Transcriptoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA