Influence of the A and B subunits of cholera toxin (CT) and Escherichia coli toxin (LT) on TNF-α release from macrophages

Domingos, Marta O.; Andrade, R.G.; Barbaro, K.C.; Borges, Monamaris Marques; Lewis, David J. M.; New, R. R. C.

doi:10.1016/j.toxicon.2008.12.017

Cited by 11 publications

(5 citation statements)

References 18 publications

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“…Studies in vitro have demonstrated that CT suppresses induction of proinflammatory and regulatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-6 (IL-6), and IL-12 by lipopolysaccharide (LPS)-stimulated macrophages (6,10). CT is also known to be a potent adjuvant, enhancing antigen presentation by antigen-presenting cells and intestinal epithelial cells (3,4,8).…”

mentioning

confidence: 99%

Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

Queen

Satchell

2012

Infect Immun

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Cholera is classically considered a noninflammatory diarrheal disease, in comparison to invasive enteric organisms, although there is a low-level proinflammatory response during early infection with Vibrio cholerae and a strong proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host defense to infection. Nontoxigenic El Tor O1 V. cholerae infection is characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha in the intestine, indicating an acute innate immune response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to decreased survival of mice. The role of neutrophils in protection of the host is to limit the infection to the intestine and control bacterial spread to extraintestinal organs. In the absence of neutrophils, the infection spread to the spleen and led to increased systemic levels of IL-1␤ and tumor necrosis factor alpha, suggesting the decreased survival in neutropenic mice is due to systemic shock. Neutrophils were found not to contribute to either clearance of colonizing bacteria or to alter the local immune response. However, when genes for secreted accessory toxins were deleted, the colonizing bacteria were cleared from the intestine, and this clearance is dependent upon neutrophils. Thus, the requirement for accessory toxins in virulence is negated in neutropenic mice, which is consistent with a role of accessory toxins in the evasion of innate immune cells in the intestine. Overall, these data support that neutrophils impact disease progression and suggest that neutrophil effectiveness can be manipulated through the deletion of accessory toxins. G lobal pandemics of the diarrheal disease cholera have occurred throughout human history. The disease is caused by ingestion of the Gram-negative bacterium Vibrio cholerae in contaminated water. Cholera is typified by symptoms of severe, watery diarrhea that leads to life-threatening dehydration and loss of electrolytes (48). There have been seven cholera pandemics in recorded history. The first six were caused by V. cholerae O1 of the classical biotype. The seventh and currently ongoing pandemic began in 1961, when V. cholerae O1 strains of the El Tor biotype began to predominate and spread throughout the world (22). Recent whole-genome analysis of single-nucleotide polymorphisms revealed that the seventh pandemic consists of three distinct waves of transmission from the pandemic center in South Asia. Strain diversification has resulted from continuous local evolution punctuated by sporadic long-range transmission to countries where this pathogen is not endemic, such as in the case of Haiti in 2010 (34). It is estimated that 1.4 billion people worldwide are at risk for cholera, with approximately 2.8 million cholera cases occurring in areas of endemicity each year (1).The innate immune response to V. cholerae infection is poorly understood. Recent studies i...

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confidence: 99%

Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

Queen

Satchell

2012

Infect Immun

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“…The B subunits of LT-IIa and LT-IIb induce the production of IL-8, IL-6, IL-1β, and TNF-α by monocytes [64]. LTB also has the ability to induce high levels of TNF-α production by murine macrophages [65]. The other cell type of major interest is the dendritic cell, which is thought to be an arena for toxin subunit adjuvant activity.…”

Section: Heat Labile Enterotoxin From Enterotoxigenic E Coli (Lt)mentioning

confidence: 99%

AB Toxins: A Paradigm Switch from Deadly to Desirable

Odumosu

Nicholas

Yano

et al. 2010

Toxins

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To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.

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“…It is believed that 1.4 billion people are at risk for cholera, and 2.8 million cases of cholera take place in endemic regions annually [2]. In addition, it is estimated that cholera contributes to as many as 120,000 deaths every year [3].…”

Section: Introductionmentioning

confidence: 99%

“…The non-toxic B subunit pentamer binds to GM1 ganglioside on intestinal epithelial cells and facilitates entry of the A subunit into cells [8], provoking massive secretion of electrolytes and water into the intestinal lumen, resulting in extensive diarrhea [5]. CT is also known to regulate immune responses by suppressing pro-inflammatory responses such as the induction of interleukin (IL)-6, IL-12, and tumor necrosis factor-a [2,6]. In contrast, it has been reported that elevated pro-inflammatory cellular immune responses have been observed in the blood and intestinal mucosa of cholera patients [9].…”

Section: Introductionmentioning

confidence: 99%

Protein profiles in mucosal and systemic compartments in response to Vibrio cholerae in a mouse pulmonary infection model

Kang

Baik

Yang

et al. 2015

Microbial Pathogenesis

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Influence of the A and B subunits of cholera toxin (CT) and Escherichia coli toxin (LT) on TNF-α release from macrophages

Cited by 11 publications

References 18 publications

Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

AB Toxins: A Paradigm Switch from Deadly to Desirable

Protein profiles in mucosal and systemic compartments in response to Vibrio cholerae in a mouse pulmonary infection model

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