Bacteriologic and histologic features in mice after intranasal inoculation of Brucella melitensis

Mg, Mense; Ll, Van De Verg; Ak, Bhattacharjee; Jl, Garrett; Ja, Hart; Le, Lindler; Tl, Hadfield; Dl, Hoover

doi:10.2460/ajvr.2001.62.398

Cited by 38 publications

(45 citation statements)

References 30 publications

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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: Discussionsupporting

confidence: 78%

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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Section: Discussionsupporting

confidence: 78%

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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“…Brucella establishes a stealthy infection in mice and constitutes an interesting experimental model that can be used to analyze the relationships between hosts and intracellular stealth pathogens (46,47). Although the aerosol route is a common cause of infection in nature (1), a relatively limited number of Brucella studies (20,22,36,37,48,49) investigated the protective immune response following respiratory infection. In this study, we analyzed the progression of B. melitensis in the lungs, spleen, and liver of C57BL/6 mice, as well as the nature of the protective immune response following primary and secondary i.n.…”

Section: Discussionmentioning

confidence: 99%

“…infection was analyzed previously by several research groups (22,36,37). However, because the infectious dose, the origin of the mice, and the conditions in the animal facility could influence the course of the infection, we began by establishing the kinetics of infection under our laboratory conditions.…”

Section: Intranasal Inoculation Leads To Slow Dissemination Of Brucelmentioning

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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“…The genotypes G1, G4, G7, G8, G9, and G10, comprising branch 1 of the dendrogram drawn for the Peruvian isolates, were isolated almost exclusively from adult patients, and a relatively high proportion of the patients infected with the four genotypes G2, G3, G5, and G6 comprising branch 2 presented with splenomegaly and/or hepatomegaly. Studies of mice may help to elucidate differences in organ tropism and pathological effects (30).…”

Section: Gender and Risk Of Infectionmentioning

confidence: 99%

Molecular Epidemiology of Brucella Genotypes in Patients at a Major Hospital in Central Peru

et al. 2009

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The multiple-locus variable-number repeat analysis of 90 human Brucella melitensis isolates from a large urban area in central Peru revealed variations at 4 (Bruce07, Bruce09, Bruce18, and Bruce42) out of 16 loci investigated, of which 1 (Bruce42) also is used for species identification. Ten genotypes were identified, separated by the number of Bruce42 repeats into two groups that may have distinct phenotypic characteristics. Whereas genotypes with five or six Bruce42 repeats were cultured mainly from adult patients, genotypes with three Bruce42 repeats were isolated from children and young adolescents as well as from adults. In addition, the isolates with three Bruce42 repeats were obtained more often from patients with splenomegaly (P ‫؍‬ 0.02) or hepatomegaly (P ‫؍‬ 0.006). An annual variation in the diversity of genotypes was observed, possibly reflecting changes in sources of fresh dairy products, supply routes to city shops and markets, and the movement of infected dairy goat herds.

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Bacteriologic and histologic features in mice after intranasal inoculation of Brucella melitensis

Abstract: Changes in the spleen and liver increased with increases in dose and with increased time following intranasal inoculation with B melitensis 16M. Surprisingly, histologic changes were not observed in the lungs of inoculated mice.

Cited by 38 publications

References 30 publications

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

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

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

Molecular Epidemiology of Brucella Genotypes in Patients at a Major Hospital in Central Peru

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