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The First Line of Defense

View Article: PubMed Central

ABSTRACT

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a “second hit” from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma.

No MeSH data available.


Related in: MedlinePlus

Intestinal CD4+ T-cell differentiation. Antigen-loaded dendritic cells (DCs) interact with naïve CD4+ T cells (yellow) in mesenteric lymph nodes through MHC-II molecules. DCs secrete different cytokines depending on this interaction. Following alcohol and burn injury, antigen-presenting cells (APCs) such as DCs may have a significantly altered cytokine expression profile. The cytokine profiles present lead to the expression of different transcription factors that promote differentiation of T cells into either Th17 (red), Th1 (blue), Th2 (green), or Treg (orange) phenotypes. These T-cell subsets secrete different cytokines that lead to inflammatory or immunosuppressive immune responses. Combined alcohol and burn injury has been shown to suppress T-cell cytokines including interferon (IFN)-γ, interleukin (IL)-17, and IL-22 from T cells.
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f3-arcr-37-2-209: Intestinal CD4+ T-cell differentiation. Antigen-loaded dendritic cells (DCs) interact with naïve CD4+ T cells (yellow) in mesenteric lymph nodes through MHC-II molecules. DCs secrete different cytokines depending on this interaction. Following alcohol and burn injury, antigen-presenting cells (APCs) such as DCs may have a significantly altered cytokine expression profile. The cytokine profiles present lead to the expression of different transcription factors that promote differentiation of T cells into either Th17 (red), Th1 (blue), Th2 (green), or Treg (orange) phenotypes. These T-cell subsets secrete different cytokines that lead to inflammatory or immunosuppressive immune responses. Combined alcohol and burn injury has been shown to suppress T-cell cytokines including interferon (IFN)-γ, interleukin (IL)-17, and IL-22 from T cells.

Mentions: Beyond the physical barrier, the next line of defense against invading pathogens is the immune system within the gut, which has the most difficult task in the body. Not only does it protect the host from invading pathogens, but it also maintains homeostasis with the vastly diverse microbiome within the intestinal lumen. The immune system must distinguish between commensal and pathogenic bacteria so that it does not mount a damaging autoimmune inflammatory response. The immune cells that carry out these tasks comprise parts of both innate and acquired immune functions. They can be found in all areas of the intestines, especially in regions called gut associated lymphoid tissue (GALT). GALT includes the gut epithelium, PPs, MLNs, and LP (Choudhry et al. 2004; Mowat and Viney 1997). Intestinal T cells are found in GALT sites and exist closely with antigen presenting cells (APCs), such as DCs and macrophages, that aid in T cell differentiation and activation (figure 3). Scientists are beginning to define the roles of macrophages and DCs in gut immune functions following alcohol exposure or trauma, as well as the initial innate immune responses that occur following these insults. These immune cells activate or suppress one another using highly complex chemical signaling pathways that researchers are beginning to uncover. Alcohol could produce disruptive effects at any point along these pathways (see figure 3).


The First Line of Defense
Intestinal CD4+ T-cell differentiation. Antigen-loaded dendritic cells (DCs) interact with naïve CD4+ T cells (yellow) in mesenteric lymph nodes through MHC-II molecules. DCs secrete different cytokines depending on this interaction. Following alcohol and burn injury, antigen-presenting cells (APCs) such as DCs may have a significantly altered cytokine expression profile. The cytokine profiles present lead to the expression of different transcription factors that promote differentiation of T cells into either Th17 (red), Th1 (blue), Th2 (green), or Treg (orange) phenotypes. These T-cell subsets secrete different cytokines that lead to inflammatory or immunosuppressive immune responses. Combined alcohol and burn injury has been shown to suppress T-cell cytokines including interferon (IFN)-γ, interleukin (IL)-17, and IL-22 from T cells.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590618&req=5

f3-arcr-37-2-209: Intestinal CD4+ T-cell differentiation. Antigen-loaded dendritic cells (DCs) interact with naïve CD4+ T cells (yellow) in mesenteric lymph nodes through MHC-II molecules. DCs secrete different cytokines depending on this interaction. Following alcohol and burn injury, antigen-presenting cells (APCs) such as DCs may have a significantly altered cytokine expression profile. The cytokine profiles present lead to the expression of different transcription factors that promote differentiation of T cells into either Th17 (red), Th1 (blue), Th2 (green), or Treg (orange) phenotypes. These T-cell subsets secrete different cytokines that lead to inflammatory or immunosuppressive immune responses. Combined alcohol and burn injury has been shown to suppress T-cell cytokines including interferon (IFN)-γ, interleukin (IL)-17, and IL-22 from T cells.
Mentions: Beyond the physical barrier, the next line of defense against invading pathogens is the immune system within the gut, which has the most difficult task in the body. Not only does it protect the host from invading pathogens, but it also maintains homeostasis with the vastly diverse microbiome within the intestinal lumen. The immune system must distinguish between commensal and pathogenic bacteria so that it does not mount a damaging autoimmune inflammatory response. The immune cells that carry out these tasks comprise parts of both innate and acquired immune functions. They can be found in all areas of the intestines, especially in regions called gut associated lymphoid tissue (GALT). GALT includes the gut epithelium, PPs, MLNs, and LP (Choudhry et al. 2004; Mowat and Viney 1997). Intestinal T cells are found in GALT sites and exist closely with antigen presenting cells (APCs), such as DCs and macrophages, that aid in T cell differentiation and activation (figure 3). Scientists are beginning to define the roles of macrophages and DCs in gut immune functions following alcohol exposure or trauma, as well as the initial innate immune responses that occur following these insults. These immune cells activate or suppress one another using highly complex chemical signaling pathways that researchers are beginning to uncover. Alcohol could produce disruptive effects at any point along these pathways (see figure 3).

View Article: PubMed Central

ABSTRACT

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen. The intestinal barrier is compromised following alcohol exposure, which can lead to life-threatening systemic complications including sepsis and multiple organ failure. Furthermore, alcohol is a major confounding factor in pathology associated with trauma. Experimental data from both human and animal studies suggest that alcohol perturbs the intestinal barrier and its function, which is exacerbated by a “second hit” from traumatic injury. This article highlights the role of alcohol-mediated alterations of the intestinal epithelia and its defense against bacteria within the gut, and the impact of alcohol on intestinal immunity, specifically on T cells and neutrophils. Finally, it discusses how the gut microbiome both contributes to and protects the intestines from dysbiosis after alcohol exposure and trauma.

No MeSH data available.


Related in: MedlinePlus