Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis

Noor, Zannatun; Watanabe, Kôji; Abhyankar, Mayuresh M.; Burgess, Stacey L.; Buonomo, Erica L.; Cowardin, Carrie A.; Petri, William A.

doi:10.1128/mbio.02329-16

Cited by 16 publications

(19 citation statements)

References 38 publications

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“…Recently, we reported that IL-25 mediated mucosal barrier function plays an important role in the protection from intestinal E . histolytica infection [ 24 ]. Also, it is known that secretion of IL-25 could be reduced by antibiotic induced dysbiosis [ 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

Watanabe

Gilchrist

et al. 2017

PLoS Pathog

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The disease severity of Entamoeba histolytica infection ranges from asymptomatic to life-threatening. Recent human and animal data implicate the gut microbiome as a modifier of E. histolytica virulence. Here we have explored the association of the microbiome with susceptibility to amebiasis in infants and in the mouse model of amebic colitis. Dysbiosis occurred symptomatic E. histolytica infection in children, as evidenced by a lower Shannon diversity index of the gut microbiota. To test if dysbiosis was a cause of susceptibility, wild type C57BL/6 mice (which are innately resistant to E. histiolytica infection) were treated with antibiotics prior to cecal challenge with E. histolytica. Compared with untreated mice, antibiotic pre-treated mice had more severe colitis and delayed clearance of E. histolytica. Gut IL-25 and mucus protein Muc2, both shown to provide innate immunity in the mouse model of amebic colitis, were lower in antibiotic pre-treated mice. Moreover, dysbiotic mice had fewer cecal neutrophils and myeloperoxidase activity. Paradoxically, the neutrophil chemoattractant chemokines CXCL1 and CXCL2, as well as IL-1β, were higher in the colon of mice with antibiotic-induced dysbiosis. Neutrophils from antibiotic pre-treated mice had diminished surface expression of the chemokine receptor CXCR2, potentially explaining their inability to migrate to the site of infection. Blockade of CXCR2 increased susceptibility of control non-antibiotic treated mice to amebiasis. In conclusion, dysbiosis increased the severity of amebic colitis due to decreased neutrophil recruitment to the gut, which was due in part to decreased surface expression on neutrophils of CXCR2.

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Section: Resultsmentioning

confidence: 99%

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

Watanabe

Gilchrist

et al. 2017

PLoS Pathog

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“…In the present work, where immunization by a unique helminth protein (P28GST) alters the susceptibility of mice to colitis in a preventive manner, we previously demonstrated that such anti-inflammatory effects encompass the contribution of mucosal eosinophils, acting as T-helper-type (Th2) response inducers [7]. In addition to systemic and local induction of IL-13 and IL-5, a possible role of IL-25 can be hypothesized, as it has recently been shown in protection from amoebic colitis, acting via eosinophils and suppression of TNF-α through a new pathway of innate mucosal immune response [39].…”

Section: Discussionmentioning

confidence: 99%

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights

Foligné

Plé

Titécat

et al. 2019

Cells

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An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn’s disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn’s disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.

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“…139). For host defence responses to non-classical microbial targets, eosinophil-derived IL-25 helps to mediate protection from protozoan parasite-elicited amoebic colitis 140 , and eosinophils, as sources of IL-23 and IL-17, are immunomodulatory in fungal aspergillosis 141 . In response to systemic IL-33 administration, ILC2-derived IL-5 and the associated eosinophil recruitment have both been shown to promote increased pulmonary artery hypertrophy, which is a previously unrecognized role for eosinophils 142 .…”

Section: Eosinophils In Other Host Responsesmentioning

confidence: 99%

Functions of tissue-resident eosinophils

2017

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Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, ‘non-effector’ functions in health and disease.

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Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis

Cited by 16 publications

References 38 publications

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights

Functions of tissue-resident eosinophils

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