Pathologic changes associated with brucellosis experimentally induced by aerosol exposure in rhesus macaques ( Macaca mulatta )

Mense, Mark G.; Borschel, Richard; Wilhelmsen, Catherine L.; Pitt, M. Louise M.; Hoover, David L.

doi:10.2460/ajvr.2004.65.644

Cited by 43 publications

(51 citation statements)

References 22 publications

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“…Aerosol chambers have been successfully used to study infections with several different organisms, including Mycobacterium tuberculosis, Bacillus anthracis, and Coxiella burnetti in mice and guinea pigs (11,16,(25)(26)(27). Aerosol exposure has also been utilized previously to infect rhesus macaques with B. melitensis, but this is the first evaluation of aerosol infection in mice, which have been widely used to model human infections (17).…”

Section: Discussionmentioning

confidence: 99%

“…Abattoir workers may also acquire the disease via aerosol exposure (2, 3, 13-15, 18, 31). The Brucella species most pathogenic to humans include Brucella melitensis, B. suis, B. abortus, and B. canis, all of which are distributed worldwide but are most common in Mediterranean countries, the Middle East, India, Mexico, Central Asia, and Central and South America (3,10,13,17,22,23). Brucellosis has been reported to be the most common zoonotic infection worldwide, with over 500,000 new infections reported annually (22,23).…”

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confidence: 99%

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Aerosol Infection of BALB/c Mice with Brucella melitensis and Brucella abortus and Protective Efficacy against Aerosol Challenge

2007

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Brucellosis is a zoonotic disease with a worldwide distribution that can be transmitted via intentional or accidental aerosol exposure. In order to engineer superior vaccine strains against Brucella species for use in animals as well as in humans, the possibility of challenge infection via aerosol needs to be considered to properly evaluate vaccine efficacy. In this study, we assessed the use of an aerosol chamber to infect deep lung tissue of mice to elicit systemic infections with either Brucella abortus or B. melitensis at various doses. The results reveal that B. abortus causes a chronic infection of lung tissue in BALB/c mice and peripheral organs at low doses. In contrast, B. melitensis infection diminishes more rapidly, and higher infectious doses are required to obtain infection rates in animals similar to those of B. abortus. Whether this difference translates to severity of human infection remains to be elucidated. Despite these differences, unmarked deletion mutants BA⌬asp24 and BM⌬asp24 consistently confer superior protection to mice against homologous and heterologous aerosol challenge infection and should be considered viable candidates as vaccine strains against brucellosis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Aerosol Infection of BALB/c Mice with Brucella melitensis and Brucella abortus and Protective Efficacy against Aerosol Challenge

2007

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“…The organism is easily aerosolized and has a low infectious dose (8,9). Aerosol exposure during routine manipulation of unidentified Brucella isolates outside a BSC is the most common source of laboratory-acquired brucellosis (LAB) (7).…”

Section: Cases 3 Andmentioning

confidence: 99%

Review of Brucellosis Cases from Laboratory Exposures in the United States in 2008 to 2011 and Improved Strategies for Disease Prevention

et al. 2013

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“…Aerosol or intranasal (i.n.) exposure of mice (20) or macaques (21) to low (10 2 -10 3 ) doses of virulent B. melitensis 16M caused chronic pulmonary infection, followed by systemic infection of the spleen and liver. Interestingly, the TLRs involved in the control of Brucella following i.n.…”

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confidence: 99%

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Mambres

Machelart

Potemberg

et al. 2016

The Journal of Immunology

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The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis. Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35−/− mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35– and IL-17A–dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4+ and CD8+ α/β+ T cells are sufficient to mount a protective immune response and that an IL-17A–mediated response can compensate for the partial deficiency of an IFN-γ–mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ–and IL-17RA–mediated responses in the control of mucosal infection by Brucella.

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Pathologic changes associated with brucellosis experimentally induced by aerosol exposure in rhesus macaques ( Macaca mulatta )

Abstract: These results may aid in the development of a vaccine against brucellosis that can be used in humans.

Cited by 43 publications

References 22 publications

Aerosol Infection of BALB/c Mice with Brucella melitensis and Brucella abortus and Protective Efficacy against Aerosol Challenge

Aerosol Infection of BALB/c Mice with Brucella melitensis and Brucella abortus and Protective Efficacy against Aerosol Challenge

Review of Brucellosis Cases from Laboratory Exposures in the United States in 2008 to 2011 and Improved Strategies for Disease Prevention

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

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