Abstract
BackgroundOnly limited information is available about the immunopathogenic properties of Arcobacter infection in vivo. Therefore, we performed a meta-analysis of published data in murine infection models to compare the pathogenic potential of Arcobacter butzleri with Campylobacter jejuni and commensal Escherichia coli as pathogenic and harmless reference bacteria, respectively.Methodology / Principal FindingsGnotobiotic IL-10-/- mice generated by broad-spectrum antibiotic compounds were perorally infected with A. butzleri (strains CCUG 30485 or C1), C. jejuni (strain 81-176) or a commensal intestinal E. coli strain. Either strain stably colonized the murine intestines upon infection. At day 6 postinfection (p.i.), C. jejuni infected mice only displayed severe clinical sequelae such as wasting bloody diarrhea. Gross disease was accompanied by increased numbers of colonic apoptotic cells and distinct immune cell populations including macrophages and monocytes, T and B cells as well as regulatory T cells upon pathogenic infection. Whereas A. butzleri and E. coli infected mice were clinically unaffected, respective colonic immune cell numbers increased in the former, but not in the latter, and more distinctly upon A. butzleri strain CCUG 30485 as compared to C1 strain infection. Both, A. butzleri and C. jejuni induced increased secretion of pro-inflammatory cytokines such as IFN-γ, TNF, IL-6 and MCP-1 in large, but also small intestines. Remarkably, even though viable bacteria did not translocate from the intestines to extra-intestinal compartments, systemic immune responses were induced in C. jejuni, but also A. butzleri infected mice as indicated by increased respective pro-inflammatory cytokine concentrations in serum samples at day 6 p.i.Conclusion / SignificanceA. butzleri induce less distinct pro-inflammatory sequelae as compared to C. jejuni, but more pronounced local and systemic immune responses than commensal E. coli in a strain-dependent manner. Hence, data point towards that A. butzleri is more than a commensal in vertebrate hosts.
Highlights
The gram-negative Arcobacter species belong to the Campylobacteraceae family and can be found in a plethora of habitats
In the present study we aimed to compare the immunopathological potential of A. butzeri with the gram-negative intestinal pathogen C. jejuni and a commensal E. coli strain isolated from the intestinal microbiota of a conventional mouse
Following peroral infection with comparable bacterial loads of approximately 109 colony forming units (CFU) on two consecutive days by gavage, E. coli, A. butzleri strains CCUG 30485 and C1 as well as C. jejuni were stably colonizing the intestinal tract of gnotobiotic IL-10-/- mice, as indicated by high median bacterial loads of between 108 and 109 CFU per g feces (Fig 1)
Summary
The gram-negative Arcobacter species belong to the Campylobacteraceae family and can be found in a plethora of habitats. Neither differences could be found in fecal A. butzleri prevalences between diarrheal and non-diarrheal patients, nor did patient age, sex or place of habitation correlate with A. butzleri positive results in fecal samples derived by quantitative real-time PCR [10] It is still an open and unanswered question whether Arcobacter spp. need to be regarded as ordinary commensals or rather pathogenic species. Very recently our group showed in gnotobiotic (i.e. secondary abiotic) IL-10-/- mice, a well-established murine model of C. jejuni infection, that A. butzleri induced intestinal and systemic immune responses [13, 14] These immune reponses were highly dependent on Toll-like-receptor (TLR) -4 constituting the main receptor for lipooligosaccharide (LOS) and lipopolysaccharide (LPS) from gram-negative bacteria [15, 16]. We performed a meta-analysis of published data in murine infection models to compare the pathogenic potential of Arcobacter butzleri with Campylobacter jejuni and commensal Escherichia coli as pathogenic and harmless reference bacteria, respectively
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