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Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection

Brucella species are considered a significant cause of reproductive pathology in male and female animals. Importantly, Brucella melitensis can induce reproductive disease in humans. Reproductive pathogenesis and evaluation of newly developed countermeasures against brucellosis studies have tradition...

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Autores principales: Hensel, Martha E., Stranahan, Lauren W., Edwards, John F., Arenas-Gamboa, Angela M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626965/
https://www.ncbi.nlm.nih.gov/pubmed/36338077
http://dx.doi.org/10.3389/fmicb.2022.1029199
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author Hensel, Martha E.
Stranahan, Lauren W.
Edwards, John F.
Arenas-Gamboa, Angela M.
author_facet Hensel, Martha E.
Stranahan, Lauren W.
Edwards, John F.
Arenas-Gamboa, Angela M.
author_sort Hensel, Martha E.
collection PubMed
description Brucella species are considered a significant cause of reproductive pathology in male and female animals. Importantly, Brucella melitensis can induce reproductive disease in humans. Reproductive pathogenesis and evaluation of newly developed countermeasures against brucellosis studies have traditionally utilized female animal models. However, any potential, new intervention for use in humans would need to be evaluated in both sexes. Therefore, animal models for male reproductive brucellosis are desperately needed to understand disease progression. Accordingly, we evaluated guinea pigs and mice using B. melitensis 16 M in an intratracheal model of inoculation at different stages of infection (peracute, acute, and chronic) with an emphasis on determining the effect to the male reproductive organs. Aerosol inoculation resulted in colonization of the reproductive organs (testicle, epididymis, prostate) in both species. Infection peaked during the peracute (1-week post-infection [p.i.]) and acute (2-weeks p.i.) stages of infection in the mouse in spleen, epididymis, prostate, and testicle, but colonization was poorly associated with inflammation. In the guinea pig, peak infection was during the acute stage (4-weeks p.i.) and resulted in inflammation that disrupted spermatogenesis chronically. To determine if vaccine efficacy could be evaluated using these models, males were vaccinated using subcutaneous injection with vaccine candidate 16 MΔvjbR at 10(9) CFU/100 μl followed by intratracheal challenge with 16 M at 10(7). Interestingly, vaccination efficacy varied between species and reproductive organs demonstrating the value of evaluating vaccine candidates in multiple models and sexes. Vaccination resulted in a significant reduction in colonization in the mouse, but this could not be correlated with a decrease in inflammation. Due to the ability to evaluate for both colonization and inflammation, guinea pigs seemed the better model not only for assessing host-pathogen interactions but also for future vaccine development efforts.
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spelling pubmed-96269652022-11-03 Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection Hensel, Martha E. Stranahan, Lauren W. Edwards, John F. Arenas-Gamboa, Angela M. Front Microbiol Microbiology Brucella species are considered a significant cause of reproductive pathology in male and female animals. Importantly, Brucella melitensis can induce reproductive disease in humans. Reproductive pathogenesis and evaluation of newly developed countermeasures against brucellosis studies have traditionally utilized female animal models. However, any potential, new intervention for use in humans would need to be evaluated in both sexes. Therefore, animal models for male reproductive brucellosis are desperately needed to understand disease progression. Accordingly, we evaluated guinea pigs and mice using B. melitensis 16 M in an intratracheal model of inoculation at different stages of infection (peracute, acute, and chronic) with an emphasis on determining the effect to the male reproductive organs. Aerosol inoculation resulted in colonization of the reproductive organs (testicle, epididymis, prostate) in both species. Infection peaked during the peracute (1-week post-infection [p.i.]) and acute (2-weeks p.i.) stages of infection in the mouse in spleen, epididymis, prostate, and testicle, but colonization was poorly associated with inflammation. In the guinea pig, peak infection was during the acute stage (4-weeks p.i.) and resulted in inflammation that disrupted spermatogenesis chronically. To determine if vaccine efficacy could be evaluated using these models, males were vaccinated using subcutaneous injection with vaccine candidate 16 MΔvjbR at 10(9) CFU/100 μl followed by intratracheal challenge with 16 M at 10(7). Interestingly, vaccination efficacy varied between species and reproductive organs demonstrating the value of evaluating vaccine candidates in multiple models and sexes. Vaccination resulted in a significant reduction in colonization in the mouse, but this could not be correlated with a decrease in inflammation. Due to the ability to evaluate for both colonization and inflammation, guinea pigs seemed the better model not only for assessing host-pathogen interactions but also for future vaccine development efforts. Frontiers Media S.A. 2022-10-19 /pmc/articles/PMC9626965/ /pubmed/36338077 http://dx.doi.org/10.3389/fmicb.2022.1029199 Text en Copyright © 2022 Hensel, Stranahan, Edwards and Arenas-Gamboa. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hensel, Martha E.
Stranahan, Lauren W.
Edwards, John F.
Arenas-Gamboa, Angela M.
Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title_full Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title_fullStr Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title_full_unstemmed Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title_short Intratracheal inoculation results in Brucella-associated reproductive disease in male mouse and guinea pig models of infection
title_sort intratracheal inoculation results in brucella-associated reproductive disease in male mouse and guinea pig models of infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626965/
https://www.ncbi.nlm.nih.gov/pubmed/36338077
http://dx.doi.org/10.3389/fmicb.2022.1029199
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