Comparative histopathology in BALB/c mice infected with virulent and attenuated strains of Brucella abortus

Enright, Frederick M.; Araya, Luis Nazario; Elzer, Philip H.; Rowe, G E; Winter, A J

doi:10.1016/0165-2427(90)90065-z

Cited by 58 publications

(72 citation statements)

References 24 publications

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“…MG formation (morphology and kinetics) during B. microti infection is different from that reported during B. abortus infection in mice (9,35). However, similar MG have been found during infection with B. melitensis (35), indicating that B. melitensis may be a more valid model of experimental brucellosis than B. abortus in mice.…”

Section: Resultsmentioning

confidence: 45%

Course of Infection with the Emergent Pathogen Brucella microti in Immunocompromised Mice

et al. 2011

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A new Brucella species, Brucella microti, has been isolated from wild rodents and found to be pathogenic in mice. The biological relevance of this new mouse pathogen is clear, as it allows us to study Brucella infection in a species-specific model. The course of infection in wild-type (wt) and immunodeficient mice that lack B (Jh), T and B (SCID), or T, B, and NK (SCID.Beige) cells was analyzed over 3 weeks. wt mice completely cleared bacteria from the liver and spleen after that time. However, SCID mice showed a much higher bacterial load in the spleen and liver than wt and Jh mice after 1 week and maintained the same level during the next 2 weeks. All mice tested survived for the 3 weeks. In contrast, the bacterial levels in mice that lacked NK cell activity progressively increased and these mice succumbed to infection after 16 to 18 days. Histopathology analysis of infected mice showed extensive areas of necrotic tissue and thrombosis in liver after 1 week in all infected SCID.Beige mice but were not seen in either SCID or wt animals. These processes were dramatically increased after 21 days, corresponding with the death of SCID.Beige animals. Our results indicate that T and/or B cells are required for the control of infection with the mouse pathogen Brucella microti in liver and spleen but that NK cells are crucial for survival in the absence of B and T cells. In addition, they suggest that controlled granuloma formation is critical to clear this type of infection in wt mice.Members of the genus Brucella are Gram-negative coccobacilli that are considered facultative intracellular pathogens capable of infecting a variety of hosts, including mammals such as rodents and humans. Infection causes a chronic disease termed brucellosis, the most important worldwide zoonosis (12). The genus consists of several species, differing from each other on the basis of the specific host they invade. To date, there are at least nine recognized species of Brucella; most of them are able to cause disease in humans (Brucella melitensis, Brucella canis, Brucella pinnipedialis, Brucella inopinata, Brucella ceti, Brucella suis and Brucella abortus), while the others are able to cause diseases in nonhuman hosts (Brucella ovis and Brucella neotomae) (14, 26) (17, 33).The interaction between Brucella spp. and the host immune system is a complex process during which bacteria colonize host macrophages by developing a number of strategies to hide from and avoid the host immune response, establishing a chronic infection (2, 17, 31). With B. abortus and B. melitensis, some key cellular components of the host immunity system have been found to be important for the control and clearance of this infection in mouse models (16). Among them, dendritic cells and macrophages (6,21,27) Recently, a new species of Brucella, called Brucella microti, has been identified in and isolated from the common vole, Microtus arvalis, a small rodent with widespread distribution in Europe and Asia (1, 30). B. microti has also been identified in the red fox and so...

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Section: Resultsmentioning

confidence: 45%

Course of Infection with the Emergent Pathogen Brucella microti in Immunocompromised Mice

et al. 2011

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“…In addition, in this study, neither neutrophil influx nor significant histopathological changes were observed in the ileum or colon. Conversely, histopathological lesions observed in the spleen and liver, including neutrophilic infiltrate and granulomas were similar to the lesions described in mice inoculated by other routes of infection (19,36).…”

Section: Discussionmentioning

confidence: 51%

Establishment of Systemic Brucella melitensis Infection through the Digestive Tract Requires Urease, the Type IV Secretion System, and Lipopolysaccharide O Antigen

Paixão

Roux²,

Hartigh³

et al. 2009

Infect Immun

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Human brucellosis is caused mainly by Brucella melitensis, which is often acquired by ingesting contaminated goat or sheep milk and cheese. Bacterial factors required for food-borne infection of humans by B. melitensis are poorly understood. In this study, a mouse model of oral infection was characterized to assess the roles of urease, the VirB type IV secretion system, and lipopolysaccharide for establishing infection through the digestive tract. B. melitensis strain 16M was consistently recovered from the mesenteric lymph node (MLN), spleen, and liver beginning at 3 or 7 day postinfection (dpi). In the gut, persistence of the inoculum was observed up to 21 dpi. No inflammatory lesions were observed in the ileum or colon during infection. Mutant strains lacking the ureABC genes of the ure1 operon, virB2, or pmm encoding phosphomannomutase were constructed and compared to the wild-type strain for infectivity through the digestive tract. Mutants lacking the virB2 and pmm genes were attenuated in the spleen (P < 0.05) and MLN (P < 0.001), respectively. The wild-type and mutant strains had similar levels of resistance to low pH and 5 or 10% bile, suggesting that the reduced colonization of mutants was not the result of reduced resistance to acid pH or bile salts. In an in vitro lymphoepithelial cell (M-cell) model, B. melitensis transited rapidly through polarized enterocyte monolayers containing M-like cells; however, transit through monolayers containing only enterocytes was reduced or absent. These results indicate that B. melitensis is able to spread systemically from the digestive tract after infection, most likely through M cells of the mucosa-associated lymphoid tissue.Brucella spp. are facultative intracellular gram-negative bacteria that cause chronic infections in mammalian hosts. Brucella melitensis infects mainly goats and sheep, causing abortion, placentitis, and infertility, and it is considered the most pathogenic species of Brucella to humans (15). Human brucellosis is an important worldwide zoonosis that causes social and economic impacts on public health and animal production. The disease is prevalent mostly in the Middle East, Mediterranean, Central Asia, Latin America, and North Africa, with over 500,000 new cases of human brucellosis registered annually (41).Human brucellosis usually does not present with specific clinical symptoms. It is frequently associated with intermittent fever, anorexia, weakness, soreness, and inflammation affecting several organs. Spondylitis, arthritis, osteomyelitis, and epididymo-orchitis are common manifestations of the infection. However, infection of the heart and brain may also occur and can result in death (34). Human brucellosis caused by B. melitensis results mostly from ingestion of unpasteurized milk and dairy products from infected goats, sheep, camels, and cattle. The importance of food-borne infection is underlined by a recent study in Mexico, which reported that in 98% of cases, the major risk factor for brucellosis was ingestion of contaminated dairy p...

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“…and intravenous routes also revealed a more persistent and chronic infection with B. abortus than with B. melitensis (6,7,9,15,21). Although the present studies considered time points up to only 8 weeks postinfection, a similar trend was observed with the aerosol exposure described here.…”

Section: Discussionmentioning

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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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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Comparative histopathology in BALB/c mice infected with virulent and attenuated strains of Brucella abortus

Cited by 58 publications

References 24 publications

Course of Infection with the Emergent Pathogen Brucella microti in Immunocompromised Mice

Course of Infection with the Emergent Pathogen Brucella microti in Immunocompromised Mice

Establishment of Systemic Brucella melitensis Infection through the Digestive Tract Requires Urease, the Type IV Secretion System, and Lipopolysaccharide O Antigen

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

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