TY - JOUR
T1 - Nlrp6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of brucella abortus
AU - Rungue, Marcella
AU - Melo, Victor
AU - Martins, David
AU - Campos, Priscila C.
AU - Leles, Gabriela
AU - Galvão, Izabela
AU - Mendes, Viviani
AU - Aganetti, Mariana
AU - Pedersen, Ágatha
AU - Assis, Natan R.G.
AU - Santos, Raiany
AU - Cassali, Geovanni D.
AU - Godard, Ana Lúcia B.
AU - Martins, Flaviano S.
AU - Oliveira, Sergio C.
AU - Vieira, Angélica T.
N1 - Publisher Copyright:
© 2021 Rungue et al.
PY - 2021/2
Y1 - 2021/2
N2 - Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infec-tion—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-contain-ing-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.
AB - Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infec-tion—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-contain-ing-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.
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U2 - 10.1371/journal.pntd.0009171
DO - 10.1371/journal.pntd.0009171
M3 - Article
C2 - 33617596
AN - SCOPUS:85102608598
SN - 1935-2727
VL - 15
SP - 1
EP - 22
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 2
M1 - e0009171
ER -