Current Concepts of the Intestinal Microbiota and the Pathogenesis of Infection

Wardwell, Leslie H.; Huttenhower, Curtis; Garrett, Wendy S.

doi:10.1007/s11908-010-0147-7

Cited by 89 publications

(63 citation statements)

References 50 publications

(61 reference statements)

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“…Regulation of T-cell death through suppression of Erdr1 by microbial products would promote T-cell survival and enhance host fitness by poising the immune system to fend off pathogens. Supporting this, germfree animals, which have elevated levels of Erdr1 and reduced T cells, are susceptible to a myriad of pathogenic infections (36,37). In contrast, excessive reduction of Erdr1 may have pathological consequences by promoting the survival of auto-reactive T lymphocytes and consequently setting the stage for autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor

Soto

Petersen

Novis

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Symbiotic microbes impact the severity of a variety of diseases through regulation of T-cell development. However, little is known regarding the molecular mechanisms by which this is accomplished. Here we report that a secreted factor, Erdr1, is regulated by the microbiota to control T-cell apoptosis. Erdr1 expression was identified by transcriptome analysis to be elevated in splenic T cells from germfree and antibiotic-treated mice. Suppression of Erdr1 depends on detection of circulating microbial products by Toll-like receptors on T cells, and this regulation is conserved in human T cells. Erdr1 was found to function as an autocrine factor to induce apoptosis through caspase 3. Consistent with elevated levels of Erdr1, germfree mice have increased splenic T-cell apoptosis. RNA sequencing of Erdr1-overexpressing cells identified the up-regulation of genes involved in Fas-mediated cell death, and Erdr1 fails to induce apoptosis in Fas-deficient cells. Importantly, forced changes in Erdr1 expression levels dictate the survival of auto-reactive T cells and the clinical outcome of neuro-inflammatory autoimmune disease. Cellular survival is a fundamental feature regulating appropriate immune responses. We have identified a mechanism whereby the host integrates signals from the microbiota to control T-cell apoptosis, making regulation of Erdr1 a potential therapeutic target for autoimmune disease.

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Section: Discussionmentioning

confidence: 99%

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor

Soto

Petersen

Novis

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Some of the other potential mechanisms for CMV-associated NEC proposed in this report 15 included increased intestinal mucosal permeability, 28 enhanced proinflammatory cytokine production, [29][30][31] and alterations in the normal interactions between host cells and commensal microorganisms. 32,33 In addition to inducing proinflammatory cytokines, CMV also encodes gene products that modulate the function of host leukocytes, including T cells, neutrophils, and natural killer cells. 34,35 CMV-induced modulation of the host immune response could in turn lead to disruptions in mucosal immune homeostasis, potentiating the development of NEC.…”

Section: Figurementioning

confidence: 99%

Asymptomatic DNAemia Heralds CMV-Associated NEC: Case Report, Review, and Rationale for Preemption

et al. 2013

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Human cytomegalovirus (CMV) infection may be acquired in very low birth weight and extremely low birth weight (ELBW) infants from breast milk. The clinical relevance of such infections is uncertain. There is no consensus on whether screening breast milk for CMV, freezing/pasteurizing milk before feeding, or performing virological monitoring on at-risk infants is warranted. We describe an ELBW infant who acquired CMV postnatally from breast milk and developed CMV sepsis syndrome and clinical evidence of necrotizing enterocolitis (NEC) at ∼5 weeks of age. The availability of serial dried blood spots from day of life (DOL) 4 to 21, coincidentally obtained for a metabolic study, provided the novel opportunity to retrospectively test for and quantify the magnitude of CMV DNAemia. DNAemia was present for several weeks before the onset of severe CMV disease, first being noted on DOL 18 and increasing in magnitude daily to 4.8 log10 genomes/mL on DOL 21, approximately 8 days before the onset of abdominal distension and 15 days before the onset of CMV sepsis syndrome and NEC. After surgical resection, supportive care, and ganciclovir therapy, the infant recovered. This case underscores the importance of including CMV infection in the differential diagnosis of sepsis and NEC in premature infants. This case also suggests the value of prospective virological monitoring in at-risk low birth weight and ELBW infants. Future studies should examine the potential utility of preemptive monitoring for, and possibly treatment of, CMV DNAemia in premature infants, which may herald the onset of serious disease.

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“…Conversely, respiratory tracts contain only about 10 4 total bacteria and ample uninhabited space. A wide variety of both commensal and pathogenic organisms colonize the nasopharynx, causing infections in both the lower respiratory tract and upper respiratory tract when host homeostasis is compromised [1,2,3,4]. …”

Section: Introductionmentioning

confidence: 99%

Virus-Bacteria Interactions: An Emerging Topic in Human Infection

Almand

Moore

Jaykus

2017

Viruses

101

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Bacteria and viruses often occupy the same niches, however, interest in their potential collaboration in promoting wellness or disease states has only recently gained traction. While the interaction of some bacteria and viruses is well characterized (e.g., influenza virus), researchers are typically more interested in the location of the infection than the manner of cooperation. There are two overarching types of bacterial-virus disease causing interactions: direct interactions that in some way aid the viruses, and indirect interactions aiding bacteria. The virus-promoting direct interactions occur when the virus exploits a bacterial component to facilitate penetration into the host cell. Conversely, indirect interactions result in increased bacterial pathogenesis as a consequence of viral infection. Enteric viruses mainly utilize the direct pathway, while respiratory viruses largely affect bacteria in an indirect fashion. This review focuses on some key examples of how virus-bacteria interactions impact the infection process across the two organ systems, and provides evidence supporting this as an emerging theme in infectious disease.

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Current Concepts of the Intestinal Microbiota and the Pathogenesis of Infection

Cited by 89 publications

References 50 publications

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor

Asymptomatic DNAemia Heralds CMV-Associated NEC: Case Report, Review, and Rationale for Preemption

Virus-Bacteria Interactions: An Emerging Topic in Human Infection

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