Effect of Alcohol Consumption on Host Release of Interleukin‐17 During Pulmonary Infection With <i>Klebsiella pneumoniae</i>

Shellito, Judd E.; Zheng, Min Quan; Peng, Ye; Ruan, Sanbao; Shean, Mary K.; Kolls, Jay K.

doi:10.1111/j.1530-0277.2001.tb02293.x

Cited by 42 publications

(13 citation statements)

References 77 publications

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“…It has been established that acute and chronic alcohol intake increases the susceptibility to infections caused by bacterial and viral pathogens (33,34). The impaired host defense associated with alcohol is the consequence of a defective inflammatory response, with altered cytokine production and decreased neutrophil function (35,36).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of Human Receptors for Short Chain Fatty Acids and Their Role in Polymorphonuclear Cell Activation

Poul

Loison

Struyf

et al. 2003

Journal of Biological Chemistry

1,387

1,347

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Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 M) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca 2؉ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxinsensitive G i/o family, whereas GPR43 displayed a dual coupling through G i/o and Pertussis toxin-insensitive G q protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca 2؉ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.

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Section: Discussionmentioning

confidence: 99%

Functional Characterization of Human Receptors for Short Chain Fatty Acids and Their Role in Polymorphonuclear Cell Activation

Poul

Loison

Struyf

et al. 2003

Journal of Biological Chemistry

1,387

1,347

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“…IL-17 stimulates the epithelium to release chemokines that augment neutrophil recruitment, preventing bacterial dissemination (8). Alcoholism is linked to bacterial pneumonia, and alcohol inhibits the production of IL-23 and IL-17 following infection (95,96). Adenoviral delivery of IL-17 restores survival of ethanol-treated mice during K. pneumoniae challenge (96), demonstrating that immune pathways downstream of IL-17R signaling are intact following ethanol consumption.…”

Section: Il-17 In Lung Immunitymentioning

confidence: 99%

“…Alcoholism is linked to bacterial pneumonia, and alcohol inhibits the production of IL-23 and IL-17 following infection (95,96). Adenoviral delivery of IL-17 restores survival of ethanol-treated mice during K. pneumoniae challenge (96), demonstrating that immune pathways downstream of IL-17R signaling are intact following ethanol consumption. Dissecting the role of TLR expression by individual DC subsets can help us understand the mechanisms of innate IL-17 release during acute bacterial infections.…”

Section: Il-17 In Lung Immunitymentioning

confidence: 99%

Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense

McAleer

Kolls

2014

Immunological Reviews

169

141

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Summary Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments likely require manipulating the inflammatory response to pathogenic microbes or allergens. Here we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδT cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4+ T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL-1β and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1β and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to anti-bacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation.

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“…Historically, K. pneumoniae has been identified as a cause of severe community acquired pneumonia, known as the Friedlander syndrome, and has been found to be particularly common in alcoholics and diabetics [1], [2], [4], [5]. Its pathogenesis is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Klebsiella pneumoniae Oropharyngeal Carriage in Rural and Urban Vietnam and the Effect of Alcohol Consumption

et al. 2014

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IntroductionCommunity acquired K. pneumoniae pneumonia is still common in Asia and is reportedly associated with alcohol use. Oropharyngeal carriage of K. pneumoniae could potentially play a role in the pathogenesis of K. pneumoniae pneumonia. However, little is known regarding K. pneumoniae oropharyngeal carriage rates and risk factors. This population-based cross-sectional study explores the association of a variety of demographic and socioeconomic factors, as well as alcohol consumption with oropharyngeal carriage of K. pneumoniae in Vietnam.Methods and Findings1029 subjects were selected randomly from age, sex, and urban and rural strata. An additional 613 adult men from a rural environment were recruited and analyzed separately to determine the effects of alcohol consumption. Demographic, socioeconomic, and oropharyngeal carriage data was acquired for each subject. The overall carriage rate of K. pneumoniae was 14.1% (145/1029, 95% CI 12.0%–16.2%). By stepwise logistic regression, K. pneumoniae carriage was found to be independently associated with age (OR 1.03, 95% CI 1.02–1.04), smoking (OR 1.9, 95% CI 1.3–2.9), rural living location (OR 1.6, 95% CI 1.1–2.4), and level of weekly alcohol consumption (OR 1.7, 95% CI 1.04–2.8).ConclusionModerate to heavy weekly alcohol consumption, old age, smoking, and living in a rural location are all found to be associated with an increased risk of K. pneumoniae carriage in Vietnamese communities. Whether K. pneumoniae carriage is a risk factor for pneumonia needs to be elucidated.

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Effect of Alcohol Consumption on Host Release of Interleukin‐17 During Pulmonary Infection With Klebsiella pneumoniae

Abstract: The results of these experiments strongly implicate IL-17 as an important pathway for the immunosuppression associated with alcohol abuse and support gene therapeutic approaches to augment immune function in the alcoholic host or to treat infections associated with alcoholism.

Cited by 42 publications

References 77 publications

Functional Characterization of Human Receptors for Short Chain Fatty Acids and Their Role in Polymorphonuclear Cell Activation

Functional Characterization of Human Receptors for Short Chain Fatty Acids and Their Role in Polymorphonuclear Cell Activation

Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense

Klebsiella pneumoniae Oropharyngeal Carriage in Rural and Urban Vietnam and the Effect of Alcohol Consumption

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