Anti-inflammatory effects of the octapeptide NAP in human microbiota-associated mice suffering from subacute ileitis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.

Related collections

Most cited references 42

Record: found
Abstract: found
Article: not found

Microbial influences in inflammatory bowel diseases.

R. Sartor (2008)

The predominantly anaerobic microbiota of the distal ileum and colon contain an extraordinarily complex variety of metabolically active bacteria and fungi that intimately interact with the host's epithelial cells and mucosal immune system. Crohn's disease, ulcerative colitis, and pouchitis are the result of continuous microbial antigenic stimulation of pathogenic immune responses as a consequence of host genetic defects in mucosal barrier function, innate bacterial killing, or immunoregulation. Altered microbial composition and function in inflammatory bowel diseases result in increased immune stimulation, epithelial dysfunction, or enhanced mucosal permeability. Although traditional pathogens probably are not responsible for these disorders, increased virulence of commensal bacterial species, particularly Escherichia coli, enhance their mucosal attachment, invasion, and intracellular persistence, thereby stimulating pathogenic immune responses. Host genetic polymorphisms most likely interact with functional bacterial changes to stimulate aggressive immune responses that lead to chronic tissue injury. Identification of these host and microbial alterations in individual patients should lead to selective targeted interventions that correct underlying abnormalities and induce sustained and predictable therapeutic responses.

0 comments Cited 178 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii.

Markus M. Heimesaat, Stefan Bereswill, André Fischer … (2006)

Oral infection of susceptible mice with Toxoplasma gondii results in Th1-type immunopathology in the ileum. We investigated gut flora changes during ileitis and determined contributions of gut bacteria to intestinal inflammation. Analysis of the intestinal microflora revealed that ileitis was accompanied by increasing bacterial load, decreasing species diversity, and bacterial translocation. Gram-negative bacteria identified as Escherichia coli and Bacteroides/Prevotella spp. accumulated in inflamed ileum at high concentrations. Prophylactic or therapeutic administration of ciprofloxacin and/or metronidazole ameliorated ileal immunopathology and reduced intestinal NO and IFN-gamma levels. Most strikingly, gnotobiotic mice in which cultivable gut bacteria were removed by quintuple antibiotic treatment did not develop ileitis after Toxoplasma gondii infection. A reduction in total numbers of lymphocytes was observed in the lamina propria of specific pathogen-free (SPF), but not gnotobiotic, mice upon development of ileitis. Relative numbers of CD4(+) T cells did not differ in naive vs infected gnotobiotic or SPF mice, but infected SPF mice showed a significant increase in the frequencies of activated CD4(+) T cells compared with gnotobiotic mice. Furthermore, recolonization with total gut flora, E. coli, or Bacteroides/Prevotella spp., but not Lactobacillus johnsonii, induced immunopathology in gnotobiotic mice. Animals recolonized with E. coli and/or total gut flora, but not L. johnsonii, showed elevated ileal NO and/or IFN-gamma levels. In conclusion, Gram-negative bacteria, i.e., E. coli, aggravate pathogen-induced intestinal Th1-type immunopathology. Thus, pathogen-induced acute ileitis may prove useful to study bacteria-host interactions in small intestinal inflammation and to test novel therapies based on modulation of gut flora.

0 comments Cited 175 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Novel Murine Infection Models Provide Deep Insights into the “Ménage à Trois” of Campylobacter jejuni, Microbiota and Host Innate Immunity

Stefan Bereswill, André Fischer, Rita Plickert … (2011)

Background Although Campylobacter jejuni-infections have a high prevalence worldwide and represent a significant socioeconomic burden, it is still not well understood how C. jejuni causes intestinal inflammation. Detailed investigation of C. jejuni-mediated intestinal immunopathology is hampered by the lack of appropriate vertebrate models. In particular, mice display colonization resistance against this pathogen. Methodology/Principal Findings To overcome these limitations we developed a novel C. jejuni-infection model using gnotobiotic mice in which the intestinal flora was eradicated by antibiotic treatment. These animals could then be permanently associated with a complete human (hfa) or murine (mfa) microbiota. After peroral infection C. jejuni colonized the gastrointestinal tract of gnotobiotic and hfa mice for six weeks, whereas mfa mice cleared the pathogen within two days. Strikingly, stable C. jejuni colonization was accompanied by a pro-inflammatory immune response indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils and apoptotic cells, as well as increased concentrations of TNF-α, IL-6, and MCP-1 in the colon mucosa of hfa mice. Analysis of MyD88−/−, TRIF−/−, TLR4−/−, and TLR9−/− mice revealed that TLR4- and TLR9-signaling was essential for immunopathology following C. jejuni-infection. Interestingly, C. jejuni-mutant strains deficient in formic acid metabolism and perception induced less intestinal immunopathology compared to the parental strain infection. In summary, the murine gut flora is essential for colonization resistance against C. jejuni and can be overcome by reconstitution of gnotobiotic mice with human flora. Detection of C. jejuni-LPS and -CpG-DNA by host TLR4 and TLR9, respectively, plays a key role in immunopathology. Finally, the host immune response is tightly coupled to bacterial formic acid metabolism and invasion fitness. Conclusion/Significance We conclude that gnotobiotic and “humanized” mice represent excellent novel C. jejuni-infection and -inflammation models and provide deep insights into the immunological and molecular interplays between C. jejuni, microbiota and innate immunity in human campylobacteriosis.

0 comments Cited 123 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): 1886

Title: European Journal of Microbiology and Immunology

Abbreviated Title: EuJMI

Publisher: Akadémiai Kiadó

ISSN (Electronic): 2062-8633

Publication date (Print): June 2018

Volume: 8

Issue: 2

Pages: 34-40

Affiliations

[ ¹ ]Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Microbiology and Infection Immunology , Berlin, Germany

[ ² ]Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University , Tel Aviv, Israel

[ ³ ]Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke University Magdeburg , Magdeburg, Germany

Author notes

[*]

Corresponding author: Markus M. Heimesaat; markus.heimesaat@ 123456charite.de

[ † ]

Shared senior authorship.

Article

DOI: 10.1556/1886.2018.00006

SO-VID: a0b04dc7-7c3c-42b9-8432-a29ffdd2b144

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.

History

Date received : 17 March 2018

Date accepted : 11 April 2018

Date: 23 May 2018

Page count

Pages: 7

Comments

Comment on this article

scite_

Cited by 13

See all cited by

Most referenced authors 326

See all reference authors

The APC waiver has been extended to also apply to manuscripts submitted until March 31, 2024.

To submit to the journal, please click here.

Anti-inflammatory effects of the octapeptide NAP in human microbiota-associated mice suffering from subacute ileitis

Read this article at

Abstract

Related collections

European Journal of Microbiology and Immunology

Most cited references 42

Microbial influences in inflammatory bowel diseases.

Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii.

Novel Murine Infection Models Provide Deep Insights into the “Ménage à Trois” of Campylobacter jejuni, Microbiota and Host Innate Immunity

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 223

Cited by 13

Most referenced authors 326