NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus

Autor: Mariana Andrade Aganetti, Sergio C. Oliveira, Agatha Sondertoft Braga Pedersen, R. F. Santos, Priscila C. Campos, Angélica T. Vieira, Natan R. G. Assis, Victor Hugo Melo, Marcella Rungue, Viviani Mendes, Gabriela Leles, David Martins, Izabela Galvão, Flaviano S. Martins, Ana Lúcia Brunialti Godard, Geovanni Dantas Cassali
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
RC955-962
Administration
Oral
Brucella abortus
Gut flora
Pathology and Laboratory Medicine
Epithelium
Mice
Animal Cells
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Gastrointestinal Infections
Immune Response
Pathogen
Mice
Knockout
Gastrointestinal tract
NLRP6
biology
Fecal Microbiota Transplantation
Phenotype
Bacterial Pathogens
Anti-Bacterial Agents
Specific Pathogen-Free Organisms
Intestines
Infectious Diseases
Medical Microbiology
Physical Sciences
Host-Pathogen Interactions
Anatomy
Pathogens
Cellular Types
medicine.symptom
Public aspects of medicine
RA1-1270
Research Article
Materials Science
Material Properties
Immunology
030106 microbiology
Receptors
Cell Surface
Inflammation
Gastroenterology and Hepatology
Brucella
Microbiology
digestive system
Permeability
Brucellosis
03 medical and health sciences
Signs and Symptoms
medicine
Animals
Microbial Pathogens
Bacteria
Gut Bacteria
Organisms
Public Health
Environmental and Occupational Health
Biology and Life Sciences
Epithelial Cells
Cell Biology
biology.organism_classification
Gastrointestinal Microbiome
Gastrointestinal Tract
Mice
Inbred C57BL
Biological Tissue
030104 developmental biology
Clinical Medicine
Digestive System
Zdroj: PLoS Neglected Tropical Diseases, Vol 15, Iss 2, p e0009171 (2021)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection—Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.
Author summary Brucella abortus (Ba) is an intracellular bacterium that causes zoonotic and clinical problems worldwide. Although the common route of infection is through oral and nasal, the mechanisms toward the gastrointestinal mucosa response is still unexplored. It is well known that microbiota promotes and maintains host intestinal homeostasis during bacterial infections. However, mechanisms by which the gut microbiota affects the Ba infection have not yet been demonstrated. Here, we provide significant insights into the relationship between gut microbiota and B. abortus oral infection and demonstrate the gut microbiota contribution to the gut permeability and dissemination of Ba. Furthermore, we investigated the participation of the gut microbiota from Nlrp6 deficient mice, on the gut permeability and Ba infection. Substantial experiments performed, mostly in vivo, showed that gut microbiota alterations promote gut barrier disruption, as indicated by increased gut permeability after Ba oral infection. Thus, our work highlights the role of gut mucosal environment through gut microbiota and Nlrp6 molecule involved in host innate immune responses to Ba infection.
Databáze: OpenAIRE
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