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The Starting Lineup: Key Microbial Players in Intestinal Immunity and Homeostasis

Reading NC, Kasper DL - Front Microbiol (2011)

Bottom Line: These models have not only allowed us to tease out the roles of individual species, but have also allowed the discovery and characterization of functionally unknown organisms.Prior to linking their key role in immune system development, little was known about these organisms.Additionally, Clostridium species have most recently been shown to expand regulatory T-cell populations leading to anti-inflammatory conditions.

Affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital Boston, MA, USA.

ABSTRACT

The complexity of microbiota inhabiting the intestine is increasingly apparent. Delicate balance of numerous bacterial species can affect development of the immune system, how susceptible a host is to pathogenic organisms, and the auto-inflammatory state of the host. In the last decade, with the increased use of germ-free mice, gnotobiotic mice, and animal models in which a germ-free animal has been colonized with a foreign microbiota such as humanized mice, it has been possible to delineate relationships that specific bacteria have with the host immune system and to show what role they may play in overall host health. These models have not only allowed us to tease out the roles of individual species, but have also allowed the discovery and characterization of functionally unknown organisms. For example, segmented filamentous bacteria (SFB) have been shown to play a vital role in expansion of IL-17 producing cells. Prior to linking their key role in immune system development, little was known about these organisms. Bacteroides fragilis can rescue some of the immune defects of gnotobiotic mice after mono-colonization and have anti-inflammatory properties that can alleviate colitis and experimental allergic encephalitis in murine models. Additionally, Clostridium species have most recently been shown to expand regulatory T-cell populations leading to anti-inflammatory conditions. This review will highlight and summarize some of the major findings within the last decade concerning the role of select groups of bacteria including SFB, Clostridium, Bacteroides, Bifidobacterium, and Lactobacillus, and their impact on host mucosal immune systems.

Snapshot of bacterial–host activity in the intestine. This extremely simplistic view of intestinal activity highlights some of the major roles of different bacteria within the intestine. SFB attach to epithelial cells, induce pro-inflammatory responses, and expand TH17 cells (Davis and Savage, 1974; Gaboriau-Routhiau et al., 2009; Ivanov and Littman, 2010). Bacteroides fragilis and many Clostridium species induce IL-10 production and the expansion of T-regulatory cells (Mazmanian et al., 2005,2008; Atarashi et al., 2011). In B. fragilis, this is mediated through the surface polysaccharide, PSA (Mazmanian et al., 2008). Both Lactobacillus and Bifidobacterium can induce anti-inflammatory cytokine production, anti-microbial peptide, and mucin production, and may adhere to epithelial cells (Adlerberth et al., 1996; Pretzer et al., 2005; Kleerebezem et al., 2010; Sanchez et al., 2010; Turpin et al., 2010). The secreted proteins, p40 and p75 from many Lactobacillus species promote cell growth through a PI-3K and AKT pathway, inhibit apoptosis by causing decreased TNFα levels, and increase transepithelial resistance (TER) through increased tight junction protein production (Yan et al., 2007; Seth et al., 2008). Lactobacillus S-layer protein A (SlpA) binds to DC-SIGN which leads to increased IL-10 production. SlpA can bind directly to epithelial cells, which may play a role in colonization resistance (CR) against pathogenic bacteria (Antikainen et al., 2002; Chen et al., 2007). The Bifidobacterium serine protease inhibitor Serpin inhibits neutrophil elastase, thereby modulating acute inflammation in the intestine (Ivanov et al., 2006). Finally, undefined secreted proteins from Bifidobacterium species cause an increase in tight junction protein production and thereby TER, contributing to CR (Sanchez et al., 2010).
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Figure 1: Snapshot of bacterial–host activity in the intestine. This extremely simplistic view of intestinal activity highlights some of the major roles of different bacteria within the intestine. SFB attach to epithelial cells, induce pro-inflammatory responses, and expand TH17 cells (Davis and Savage, 1974; Gaboriau-Routhiau et al., 2009; Ivanov and Littman, 2010). Bacteroides fragilis and many Clostridium species induce IL-10 production and the expansion of T-regulatory cells (Mazmanian et al., 2005,2008; Atarashi et al., 2011). In B. fragilis, this is mediated through the surface polysaccharide, PSA (Mazmanian et al., 2008). Both Lactobacillus and Bifidobacterium can induce anti-inflammatory cytokine production, anti-microbial peptide, and mucin production, and may adhere to epithelial cells (Adlerberth et al., 1996; Pretzer et al., 2005; Kleerebezem et al., 2010; Sanchez et al., 2010; Turpin et al., 2010). The secreted proteins, p40 and p75 from many Lactobacillus species promote cell growth through a PI-3K and AKT pathway, inhibit apoptosis by causing decreased TNFα levels, and increase transepithelial resistance (TER) through increased tight junction protein production (Yan et al., 2007; Seth et al., 2008). Lactobacillus S-layer protein A (SlpA) binds to DC-SIGN which leads to increased IL-10 production. SlpA can bind directly to epithelial cells, which may play a role in colonization resistance (CR) against pathogenic bacteria (Antikainen et al., 2002; Chen et al., 2007). The Bifidobacterium serine protease inhibitor Serpin inhibits neutrophil elastase, thereby modulating acute inflammation in the intestine (Ivanov et al., 2006). Finally, undefined secreted proteins from Bifidobacterium species cause an increase in tight junction protein production and thereby TER, contributing to CR (Sanchez et al., 2010).

Mentions: In this review, we have highlighted several bacterial groups and specific species that have an immunomodulatory impact on their hosts (summarized in Figure 1). There are an incredible 1014 bacteria in the intestine and the mammalian immune system must be able to sustain these constant visitors without eliciting a strong reaction, yet at the same time, be primed to react to incoming and invading pathogens. We have described several different instances in which intestinal bacteria prime responses that mirror and enhance this vital balance by either promoting inflammatory (SFB and Th17 cells) or anti-inflammatory conditions (Clostridium, Bacteroides fragilis, Bifidobacterium, and Lactobacillus).

View Similar Images In: Results  - Collection
View Article: PubMed Central -  PubMed
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The Starting Lineup: Key Microbial Players in Intestinal Immunity and Homeostasis

Reading NC, Kasper DL - Front Microbiol (2011)

Snapshot of bacterial–host activity in the intestine. This extremely simplistic view of intestinal activity highlights some of the major roles of different bacteria within the intestine. SFB attach to epithelial cells, induce pro-inflammatory responses, and expand TH17 cells (Davis and Savage, 1974; Gaboriau-Routhiau et al., 2009; Ivanov and Littman, 2010). Bacteroides fragilis and many Clostridium species induce IL-10 production and the expansion of T-regulatory cells (Mazmanian et al., 2005,2008; Atarashi et al., 2011). In B. fragilis, this is mediated through the surface polysaccharide, PSA (Mazmanian et al., 2008). Both Lactobacillus and Bifidobacterium can induce anti-inflammatory cytokine production, anti-microbial peptide, and mucin production, and may adhere to epithelial cells (Adlerberth et al., 1996; Pretzer et al., 2005; Kleerebezem et al., 2010; Sanchez et al., 2010; Turpin et al., 2010). The secreted proteins, p40 and p75 from many Lactobacillus species promote cell growth through a PI-3K and AKT pathway, inhibit apoptosis by causing decreased TNFα levels, and increase transepithelial resistance (TER) through increased tight junction protein production (Yan et al., 2007; Seth et al., 2008). Lactobacillus S-layer protein A (SlpA) binds to DC-SIGN which leads to increased IL-10 production. SlpA can bind directly to epithelial cells, which may play a role in colonization resistance (CR) against pathogenic bacteria (Antikainen et al., 2002; Chen et al., 2007). The Bifidobacterium serine protease inhibitor Serpin inhibits neutrophil elastase, thereby modulating acute inflammation in the intestine (Ivanov et al., 2006). Finally, undefined secreted proteins from Bifidobacterium species cause an increase in tight junction protein production and thereby TER, contributing to CR (Sanchez et al., 2010).
© Copyright Policy - open-access
Figure 1: Snapshot of bacterial–host activity in the intestine. This extremely simplistic view of intestinal activity highlights some of the major roles of different bacteria within the intestine. SFB attach to epithelial cells, induce pro-inflammatory responses, and expand TH17 cells (Davis and Savage, 1974; Gaboriau-Routhiau et al., 2009; Ivanov and Littman, 2010). Bacteroides fragilis and many Clostridium species induce IL-10 production and the expansion of T-regulatory cells (Mazmanian et al., 2005,2008; Atarashi et al., 2011). In B. fragilis, this is mediated through the surface polysaccharide, PSA (Mazmanian et al., 2008). Both Lactobacillus and Bifidobacterium can induce anti-inflammatory cytokine production, anti-microbial peptide, and mucin production, and may adhere to epithelial cells (Adlerberth et al., 1996; Pretzer et al., 2005; Kleerebezem et al., 2010; Sanchez et al., 2010; Turpin et al., 2010). The secreted proteins, p40 and p75 from many Lactobacillus species promote cell growth through a PI-3K and AKT pathway, inhibit apoptosis by causing decreased TNFα levels, and increase transepithelial resistance (TER) through increased tight junction protein production (Yan et al., 2007; Seth et al., 2008). Lactobacillus S-layer protein A (SlpA) binds to DC-SIGN which leads to increased IL-10 production. SlpA can bind directly to epithelial cells, which may play a role in colonization resistance (CR) against pathogenic bacteria (Antikainen et al., 2002; Chen et al., 2007). The Bifidobacterium serine protease inhibitor Serpin inhibits neutrophil elastase, thereby modulating acute inflammation in the intestine (Ivanov et al., 2006). Finally, undefined secreted proteins from Bifidobacterium species cause an increase in tight junction protein production and thereby TER, contributing to CR (Sanchez et al., 2010).
Mentions: In this review, we have highlighted several bacterial groups and specific species that have an immunomodulatory impact on their hosts (summarized in Figure 1). There are an incredible 1014 bacteria in the intestine and the mammalian immune system must be able to sustain these constant visitors without eliciting a strong reaction, yet at the same time, be primed to react to incoming and invading pathogens. We have described several different instances in which intestinal bacteria prime responses that mirror and enhance this vital balance by either promoting inflammatory (SFB and Th17 cells) or anti-inflammatory conditions (Clostridium, Bacteroides fragilis, Bifidobacterium, and Lactobacillus).

Bottom Line: These models have not only allowed us to tease out the roles of individual species, but have also allowed the discovery and characterization of functionally unknown organisms.Prior to linking their key role in immune system development, little was known about these organisms.Additionally, Clostridium species have most recently been shown to expand regulatory T-cell populations leading to anti-inflammatory conditions.

Affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital Boston, MA, USA.

ABSTRACT

The complexity of microbiota inhabiting the intestine is increasingly apparent. Delicate balance of numerous bacterial species can affect development of the immune system, how susceptible a host is to pathogenic organisms, and the auto-inflammatory state of the host. In the last decade, with the increased use of germ-free mice, gnotobiotic mice, and animal models in which a germ-free animal has been colonized with a foreign microbiota such as humanized mice, it has been possible to delineate relationships that specific bacteria have with the host immune system and to show what role they may play in overall host health. These models have not only allowed us to tease out the roles of individual species, but have also allowed the discovery and characterization of functionally unknown organisms. For example, segmented filamentous bacteria (SFB) have been shown to play a vital role in expansion of IL-17 producing cells. Prior to linking their key role in immune system development, little was known about these organisms. Bacteroides fragilis can rescue some of the immune defects of gnotobiotic mice after mono-colonization and have anti-inflammatory properties that can alleviate colitis and experimental allergic encephalitis in murine models. Additionally, Clostridium species have most recently been shown to expand regulatory T-cell populations leading to anti-inflammatory conditions. This review will highlight and summarize some of the major findings within the last decade concerning the role of select groups of bacteria including SFB, Clostridium, Bacteroides, Bifidobacterium, and Lactobacillus, and their impact on host mucosal immune systems.

View Similar Images In: Results  - Collection
View Article: PubMed Central -  PubMed
Show All Figures - Show MeSH
getmorefigures.php?pmc=3133820&rFormat=json&query=null&req=5