Survey of small intestinal and systemic immune responses following murine Arcobacter butzleri infection

Abstract

BackgroundArcobacter (A.) butzleri has been described as causative agent for sporadic cases of human gastroenteritis with abdominal pain and acute or prolonged watery diarrhea. In vitro studies revealed distinct adhesive, invasive and cytotoxic properties of A. butzleri. Information about the underlying immunopathological mechanisms of infection in vivo, however, are scarce. The aim of this study was to investigate the immunopathological properties of two different A.butzleri strains in a well-established murine infection model.ResultsGnotobiotic IL-10−/− mice, in which the intestinal microbiota was depleted by broad-spectrum antibiotic treatment, were perorally infected with two different A. butzleri strains isolated from a diseased patient (CCUG 30485) or fresh chicken meat (C1), respectively. Eventhough bacteria of either strain could stably colonize the intestinal tract at day 6 and day 16 postinfection (p.i.), mice did not exert infection induced symptoms such as diarrhea or wasting. In small intestines of infected mice, however, increased numbers of apoptotic cells could be detected at day 16, but not day 6 following infection with either strain. A strain-dependent influx of distinct immune cell populations such as T and B cells as well as of regulatory T cells could be observed upon A. butzleri infection which was accompanied by increased small intestinal concentrations of pro-inflammatory cytokines such as TNF, IFN-γ, MCP-1 and IL-6. Remarkably, inflammatory responses following A. butzleri infection were not restricted to the intestinal tract, given that the CCUG 30485 strain induced systemic immune responses as indicated by increased IFN-γ concentrations in spleens at day 6, but not day 16 following infection.ConclusionUpon peroral infection A. butzleri stably colonized the intestinal tract of gnotobiotic IL-10−/− mice. The dynamics of distinct local and systemic inflammatory responses could be observed in a strain-dependent fashion pointing towards an immunopathogenic potential of A. butzleri in vivo. These results indicate that gnotobiotic IL-10−/− mice are well suited to further investigate the molecular mechanisms underlying arcobacteriosis in vivo.

Arcobacter: an emerging food-borne zoonotic pathogen, its public health concerns and advances in diagnosis and control – a comprehensive review

“…After oral administration of A. butzleri, the bacteria readily colonize the murine intestinal tract. However, infected mice did not show any overt clinical signs, the bacteria not only induced intestinal immune responses but also systemic immune responses in extra-intestinal places depending on the strain and time course of infection Heimesaat et al 2015a). These immune responses were TLR-4 dependent recognized by LOS and LPS derived from the cell walls of Gramnegative bacteria in gnotobiotic IL-10 -/-mice lacking TLR-4 with less pronounced intestinal and systemic immune responses Heimesaat et al 2015b;Heimesaat et al 2016).…”

“…However, infected mice did not show any overt clinical signs, the bacteria not only induced intestinal immune responses but also systemic immune responses in extra-intestinal places depending on the strain and time course of infection Heimesaat et al 2015a). These immune responses were TLR-4 dependent recognized by LOS and LPS derived from the cell walls of Gramnegative bacteria in gnotobiotic IL-10 -/-mice lacking TLR-4 with less pronounced intestinal and systemic immune responses Heimesaat et al 2015b;Heimesaat et al 2016). The mucin-2 is a pivotal constituent of the intestinal mucosa providing first line defense against intestinal pathogens (Strugala et al 2003) and was downregulated in the colon, but not in the ileum of A. butzleri infected mice (G€ olz et al 2016b;Heimesaat et al 2016).…”

Toll-like receptor-4 dependent small intestinal immune responses following murine Arcobacter butzleri infection

“…The A. butzleri reference strain CCUG 30485 was initially isolated from a fecal sample derived from a diarrheal patient [ 23 ], whereas the C1 strain was isolated from fresh chicken meat [ 10 ]. Both A. butzleri strains were grown on Karmali-Agar (Oxoid, Wesel, Germany) for 2 days at 37 °C under microaerobic conditions using CampyGen gas packs (Oxoid) as described earlier [ 20 , 21 , 26 ].…”

“…We have recently shown that, upon peroral A. butzleri infection, gnotobiotic IL-10 –/– mice with a depleted commensal microbiota following broad-spectrum antibiotic treatment [ 19 ] could be stably infected by the bacterium and displayed significant small and large intestinal pro-inflammatory immune responses [ 20 , 21 ]. Remarkably, infection-induced sequelae were not restricted to the intestinal tract, given that even systemic inflammatory responses could be observed in infected mice.…”

Toll-like receptor-4 is essential for Arcobacter butzleri-induced colonic and systemic immune responses in gnotobiotic IL-10−/− mice

“…Given that C. jejuni and A. butzleri are taxonomically related, we very recently applied the gnotobiotic IL-10 –/– mouse model to determine the pathogenic potential of A. butzleri and to investigate bacterial–host interactions in vivo . The results indicate that, upon peroral A. butzleri infection, mice could be stably colonized by the respective strains and displayed significant small and large intestinal as well as extraintestinal and systemic inflammatory responses [ 27 , 28 ].…”