The Role of ST2 Receptor in the Regulation of Brucella abortus Oral Infection.

Raiany Santos,Diego C Dos Reis,Angelica T Vieira,Flaviano Martins,Priscila C Campos,David Santos,Fabio V Marinho,Victor Rocha,Sergio C Oliveira,Viviani Mendes,Mayra F Ricci,Marcella Rungue,José Carlos Alves-Filho,Geovanni D Cassali

doi:10.3390/pathogens9050328

Abstract

The ST2 receptor plays an important role in the gut such as permeability regulation, epithelium regeneration, and promoting intestinal immune modulation. Here, we studied the role of ST2 receptor in a murine model of oral infection with Brucella abortus, its influence on gut homeostasis and control of bacterial replication. Balb/c (wild-type, WT) and ST2 deficient mice (ST2−/−) were infected by oral gavage and the results were obtained at 3 and 14 days post infection (dpi). Our results suggest that ST2−/− are more resistant to B. abortus infection, as a lower bacterial colony-forming unit (CFU) was detected in the livers and spleens of knockout mice, when compared to WT. Additionally, we observed an increase in intestinal permeability in WT-infected mice, compared to ST2−/− animals. Breakage of the intestinal epithelial barrier and bacterial dissemination might be associated with the presence of the ST2 receptor; since, in the knockout mice no change in intestinal permeability was observed after infection. Together with enhanced resistance to infection, ST2−/− produced greater levels of IFN-γ and TNF-α in the small intestine, compared to WT mice. Nevertheless, in the systemic model of infection ST2 plays no role in controlling Brucella replication in vivo. Our results suggest that the ST2 receptor is involved in the invasion process of B. abortus by the mucosa in the oral infection model.

Highlights

Brucellosis is a worldwide zoonotic disease caused by facultative intracellular pathogen of the genusBrucella [1]
The IL-33/ST2 axis is positioned to interact with the main components of the intestine, which include epithelial cells in response to cell damage and a microbiome composed of commensal bacteria and immune mucosal cells [24], we investigated the role of the ST2 receptor in the immune response against Brucella abortus oral infection
Considering that one of the main routes of the Brucella infection is through oral surfaces, we assessed the susceptibility of wild-type (WT) mice and animals deficient for the ST2 receptor (ST2−/− )

Summary

Introduction

Brucellosis is a worldwide zoonotic disease caused by facultative intracellular pathogen of the genusBrucella [1]. Bacteria of the genus Brucella infect a wide variety of land and aquatic mammals, including pigs, cattle, goats, sheep, dogs, dolphins, whales, seals, and desert wooden mice. Brucella consisted of six recognized species, grouped according to their primary host preferences, i.e., B. abortus, bovine; B. melitensis, sheep and goats; B. suis, pigs; B. ovis, sheep; B. kennels, dogs; and B. neotomae, desert wood mice. Human brucellosis can be mainly caused by Brucellaabortus and Brucella melitensis, leading to cases of morbidity and severe economic losses caused mainly by abortions and infertility in infected animals [3]. There is laboratory and occupational contamination, affecting researchers, farmers, slaughterhouse workers, butchers, and veterinary doctors (many cases of accidental self-inoculation of the vaccine against animal brucellosis), and there are forms ( very unlikely) of human transmission such as contamination of plants by feces and urine from infected animals, and breastfeeding [4,5,6,7]

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Results

Conclusion