Polysaccharide Capsules Equip the Human Symbiont <i>Bacteroides thetaiotaomicron</i> to Modulate Immune Responses to a Dominant Antigen in the Intestine

Hsieh, Samantha; Porter, Nathan T.; Donermeyer, David L.; Horváth, Stephen; Strout, Gregory W.; Saunders, Brian T.; Zhang, Nan; Zinselmeyer, Bernd H.; Martens, Eric C.; Stappenbeck, Thaddeus S.; Allen, Paul M.

doi:10.4049/jimmunol.1901206

Cited by 26 publications

(26 citation statements)

References 36 publications

(53 reference statements)

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“…These differences in phagocytosis may be partly explained by the thicknesses of the B. thetaiotaomicron CPSs as anti-stimulatory CPSs tended to be thicker than pro-stimulatory CPSs. In support of these findings, B. thetaiotaomicron expressing anti-stimulatory CPSs were cleared less effectively from the peritoneal cavity than B. thetaiotaomicron expressing pro-stimulatory CPSs in vivo, likely because anti-stimulatory CPSs inhibited uptake by peritoneal innate immune cells (24). In addition, innate immune phagocytes cultured with B. thetaiotaomicron expressing antistimulatory CPSs were poor antigen presenters to the adaptive immune system.…”

Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 70%

“…MPGs can also directly block bacterial uptake by innate immune cells, which prevents phagocytic cells from killing bacteria and antigen presenting cells from presenting antigenic peptides on the surfaces that may activate the adaptive immune system. For example, B. thetaiotaomicron with anti-stimulatory CPSs such as CPS1 are poorly uptaken by bone-marrow macrophages (BMDM) and splenic CD11c+ dendritic cells (DCs) (24). In contrast, B. thetaiotaomicron expressing prostimulatory CPSs such as CPS8 or Acap are readily phagocytosed.…”

Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 99%

“…Other MPGs protect bacteria from innate immune responses by reducing the production of pro-inflammatory cytokines by innate immune cells. Anti-stimulatory CPSs expressed on B. thetaiotaomicron decreased the levels of the pro-inflammatory cytokines IL-6 and TNF-α produced by macrophages and dendritic cells (DCs) in the presence of B. thetaiotaomicron (24). Neutrophils, macrophages, and NK cells each produced less IFN-γ, IL-12, and TNF-α in mice treated with EPS + vs. EPS − Bifidobacterium breve (B. breve) (28).…”

Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 99%

“…Salmonella Typhi capsular polysaccharide Vi repressed T cell responses by binding to T cells through the prohibitin complex and inhibiting IL-2 secretion (48). B. thetaiotaomicron expressing anti-stimulatory CPSs were also found to activate polyclonal T cells in germ-free mice more weakly than B. thetaiotaomicron expressing pro-stimulatory CPSs (24). In addition, B. fragilis PSA repressed T H 17 cell responses, which is required for B. fragilis colonization, as B. fragilis lacking PSA was unable to restrain T H 17 cell responses through TLR2 in contrast to WT B. fragilis (21).…”

Section: Mpgs Modulate Adaptive Immune Responses In the Intestinementioning

confidence: 99%

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Immunomodulatory Roles of Polysaccharide Capsules in the Intestine

Hsieh

Allen

2020

Front. Immunol.

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The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health.

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Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 70%

Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 99%

Section: Mpgs Modulate Innate Immune Responses In the Intestinementioning

confidence: 99%

Section: Mpgs Modulate Adaptive Immune Responses In the Intestinementioning

confidence: 99%

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Immunomodulatory Roles of Polysaccharide Capsules in the Intestine

Hsieh

Allen

2020

Front. Immunol.

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“…For example, just 14 sequenced strains of the common gram-negative symbiont Bacteroides thetiotaomicron harbor 47 different configurations of gene clusters for producing CPS [41]. Expression of some of these CPS alters the way this bacterium is sampled by macrophages and presented to T cells [42]. A subset of zwitterionic CPS, first discovered in Bacteroides fragilis but present in other species, has immunomodulatory properties, as do CPS and extracellular polysaccharides produced by members of different phyla, the Actinobacteria [43], Proteobacteria [44], and Firmicutes [45,46].…”

mentioning

confidence: 99%

In sickness and health: Effects of gut microbial metabolites on human physiology

Glowacki

Martens

2020

PLoS Pathog

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The connection between intestinal microbes and human health has been appreciated since the 1880s with Theodor Escherich's investigation of Escherichia coli and other fecal bacteria. Escherich hypothesized that indigenous micoorganisms play roles in both digestion and intestinal diseases [1]. In the last century, our understanding of the bacteria, viruses, archaea, and eukaryotes that normally inhabit the gut has expanded alongside the rest of the field of microbiology, and numerous fundamental roles have been established for this community, now termed the microbiome. As speculated by Escherich, these roles definitively include nutrient digestion [2, 3] and protection from invading pathogens [4] but also extend to short-and long-term instruction of the immune system [5-7] and production of a wide range of metabolites that are unable to be produced by human physiology. Although the gut microbiome is typically described as being composed of nonharmful or beneficial microorganisms, it is now appreciated that both individual species [8] or multiple community members acting together [9, 10] can exert pathogenic effects, which are often more subtle than those of classical pathogens. Indeed, the presence of common intestinal microorganisms with discrete virulence factors (e.g., enterotoxins, genotoxins) that may only manifest in diseases like colorectal cancer or inflammatory bowel disease (IBD) over long periods of time or in certain host genetic backgrounds obscures the definition of pathogen. Accelerated in the 2000s by the "-omics" revolution, along with a recent resurgence of cultivation [11-13], countless studies in the past 2 decades have implied or established connections between altered gut microbiomes and many diseases. These studies have demonstrated the malleability (or fragility) of the microbiome in the face of environmental and dietary perturbations encompassing antibiotic use [14], geography [15], immigration [16], and dietary changes, including fiber deprivation [17, 18]. Although Escherich's original ideas were logically predicted with respect to microbiome effects in the gut, less-anticipated connections between gut microbes and health have extended to neurobiology [19-22] and systemic immune responses that impact allergy [23]. Emerging studies, often extending from omics-based observations, are providing causal and mechanistic understanding of the relationships that connect host responses with changes in the microbiome and its metabolism. Here, we look at recent examples that illustrate how the gut microbiome can augment or perturb host physiology through complementary or novel metabolism often initiating or modifying disease trajectories. The studies we highlight provide details that underscore the importance of gut microbes in human health, which Escherich postulated long ago. The impact of gut bacterial metabolites on host physiology The collective diversity of microbial species that compose the gut microbiome harbor approximately 10 million unique, annotated genes [24]-probably many more [25]-that...

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Bioderived materials that disarm the gut mucosal immune system: Potential lessons from commensal microbiota

Harriman

Lewis

2021

Acta Biomaterialia

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Polysaccharide Capsules Equip the Human Symbiont Bacteroides thetaiotaomicron to Modulate Immune Responses to a Dominant Antigen in the Intestine

Abstract: This information is current as Antigen in the Intestine Modulate Immune Responses to a Dominant to Bacteroides thetaiotaomicron Symbiont Polysaccharide Capsules Equip the Human

Cited by 26 publications

References 36 publications

Immunomodulatory Roles of Polysaccharide Capsules in the Intestine

Immunomodulatory Roles of Polysaccharide Capsules in the Intestine

In sickness and health: Effects of gut microbial metabolites on human physiology

Bioderived materials that disarm the gut mucosal immune system: Potential lessons from commensal microbiota

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