Metronidazole—but not IL-10 or prednisolone—rescues Trichuris muris infected C57BL/6 IL-10 deficient mice from severe disease

Kopper, Jamie J.; Patterson, Jon S.; Mansfield, Linda S.

doi:10.1016/j.vetpar.2015.07.038

Cited by 4 publications

(8 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Outgrowth of opportunistic bacteria contributes to the mortality of IL-10 mutant mice during whipworm infection [8, 20]. Furthermore, intestinal inflammation can promote microbial dysbiosis and impair resistance to colonization by opportunistic pathogens [32, 33].…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies indicate the importance of the IL-10 receptor signalling in responses to whipworms. Specifically, IL-10 promotes host resistance and survival to whipworm infection, with IL-10 deficiency leading to morbidity and mortality that may be due to a breakdown of the epithelial barrier and the outgrowth of opportunistic bacteria [8, 20]. Mice lacking the IL-10Rα chain develop a chronic T .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

et al. 2019

View full text Add to dashboard Cite

The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intestinal epithelial cells (IECs). The IL-10 family of receptors, comprising combinations of subunits IL-10Rα, IL-10Rβ, IL-22Rα and IL-28Rα, modulates intestinal inflammatory responses. Here we carefully dissected the role of these subunits in the resistance of mice to infection with T. muris, a mouse model of the human whipworm T. trichiura. Our findings demonstrate that whilst IL-22Rα and IL-28Rα are dispensable in the host response to whipworms, IL-10 signalling through IL-10Rα and IL-10Rβ is essential to control caecal pathology, worm expulsion and survival during T. muris infections. We show that deficiency of IL-10, IL-10Rα and IL-10Rβ results in dysbiosis of the caecal microbiota characterised by expanded populations of opportunistic bacteria of the families Enterococcaceae and Enterobacteriaceae. Moreover, breakdown of the epithelial barrier after whipworm infection in IL-10, IL-10Rα and IL-10Rβ-deficient mice, allows the translocation of these opportunistic pathogens or their excretory products to the liver causing organ failure and lethal disease. Importantly, bone marrow chimera experiments indicate that signalling through IL-10Rα and IL-10Rβ in haematopoietic cells, but not IECs, is crucial to control worm expulsion and immunopathology. These findings are supported by worm expulsion upon infection of conditional mutant mice for the IL-10Rα on IECs. Our findings emphasize the pivotal and complex role of systemic IL-10Rα signalling on immune cells in promoting microbiota homeostasis and maintaining the intestinal epithelial barrier, thus preventing immunopathology during whipworm infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Infection and maintenance of T. muris was conducted as described (25). Age and sex matched female and male WT and mutant mice (6–10 wk old) were orally infected under anaesthesia with isoflurane with a high (400) or low (20–25) dose of embryonated eggs from T. muris E-isolate. Mice were randomised into uninfected and infected groups using the Graph Pad Prism randomization tool.…”

Section: Methodsmentioning

confidence: 99%

“…Resistance to infection is recapitulated by infecting mice with a high dose (200–400) of T. muris eggs and is mediated by a type-2 immune response that includes increased production of interleukin 4 (IL-4), IL-13, IL-25, IL-33, IL-9 and antibody isotypes IgG1 and IgE and results in worm expulsion (3, 7). Conversely, chronic disease is modelled by infecting mice with a low dose (20–25) of T. muris eggs that results in the development of a type-1 immune response characterised by production of inflammatory cytokines, mainly IFN-γ, and the antibody isotype IgG2a/c (3, 7). Type-1 immunity promotes intestinal inflammation that when severe can cause colitis (3, 7).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies indicate the importance of the IL-10 receptor signalling in responses to whipworms. Specifically, IL-10 promotes host resistance and survival to whipworm infection, with IL-10 deficiency leading to morbidity and mortality that may be due to a breakdown of the epithelial barrier and the outgrowth of opportunistic bacteria (8, 20). Mice lacking the IL-10Rα chain develop a chronic T. muris infection accompanied by intestinal inflammation (21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

Duque-Correa

Karp

McCarthy

et al. 2018

Preprint

View full text Add to dashboard Cite

23The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the 24 epithelium of the caecum and proximal colon of their hosts causing the human 25 disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the 26 inflammatory response elicited by the parasite while tunnelling through intestinal 27 epithelial cells (IECs). 28 The IL-10 family of receptors, comprising combinations of subunits IL-10R, IL-10R, 29 IL-22R and IL-28R, modulates intestinal inflammatory responses. Here we carefully 30 dissected the role of these subunits in the resistance of mice to infection with T. muris, 31 a mouse model of the human whipworm T. trichiura. Our findings demonstrate that 32 whilst IL-22R and IL-28R are dispensable in the host response to whipworms, IL-33 10 signalling through IL-10R and IL-10R is essential to control caecal pathology, 34 worm expulsion and survival during T. muris infections. We show that deficiency of IL-35 10, IL-10R and IL-10R results in dysbiosis of the caecal microbiota characterised 36 by expanded populations of opportunistic bacteria of the families Enterococcaceae 37 and Enterobacteriaceae. Moreover, breakdown of the epithelial barrier after whipworm 38 infection in IL-10, IL-10R and IL-10R-deficient mice, allows the translocation of 39 these opportunistic pathogens or their excretory products to the liver causing organ 40 failure and lethal disease. Importantly, bone marrow chimera experiments indicate that 41 signalling through IL-10R and IL-10R in haematopoietic cells, but not IECs, is 42 crucial to control worm expulsion and immunopathology. These findings are supported 43 by worm expulsion upon infection of conditional mutant mice for the IL-10R on IECs.

show abstract

Pre-clinical evaluation of the effect of co-medication with antibiotics and oral steroids in Göttingen Minipigs on the biological activity of the probiotic medicinal product TSO (Trichuris suis ova)

Prosberg

Kringel²,

Kapel³

et al. 2021

Parasitol Res

View full text Add to dashboard Cite

Metronidazole—but not IL-10 or prednisolone—rescues Trichuris muris infected C57BL/6 IL-10 deficient mice from severe disease

Cited by 4 publications

References 43 publications

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

Pre-clinical evaluation of the effect of co-medication with antibiotics and oral steroids in Göttingen Minipigs on the biological activity of the probiotic medicinal product TSO (Trichuris suis ova)

Contact Info

Product

Resources

About