Molecular and cellular interactions between Brucella abortus antigens and host immune responses

Oliveira, Sérgio C.; Soeurt, Nancy; Splitter, Gary A.

doi:10.1016/s0378-1135(02)00225-0

Cited by 35 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The importance of a T helper cell type 1 (Th1) response against Brucella is supported by numerous studies and is summarized elsewhere, 51,68,69 particularly the roles of CD4 þ and CD8 þ T cells, although these results were contradictory at times. Natural killer cells play an important role in some hosts, but their role was shown to be minimal in the mouse model.…”

Section: Protective Immunity Against Stealthy Brucellamentioning

confidence: 99%

Pathogenesis and Immunobiology of Brucellosis

Figueiredo

Ficht

Rice‐Ficht

et al. 2015

The American Journal of Pathology

365

270

View full text Add to dashboard Cite

This review of Brucellaehost interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion systemdependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. It is noteworthy that long ago in his publication Epidemics, Hippocrates described brucellosis-type syndromes in humans living in the Mediterranean littoral. Many centuries later, British physician, David Bruce, and Greek physician, Themistokles Zammit, in 1886 would discover the causative agent, Micrococcus melitensis, of brucellosis and would identify milk products of goats as the source of infection for military troops on the island of Malta. Even after more than a century of extensive research, Brucella spp. are still serious animal pathogens that cause brucellosis, a zoonosis that results in substantial economic losses, human morbidity, and perpetuates poverty worldwide.1 These Gram-negative bacteria infect a diverse array of land and aquatic mammals,

show abstract

Section: Protective Immunity Against Stealthy Brucellamentioning

confidence: 99%

Pathogenesis and Immunobiology of Brucellosis

Figueiredo

Ficht

Rice‐Ficht

et al. 2015

The American Journal of Pathology

365

270

View full text Add to dashboard Cite

show abstract

“…Several species of Brucella are the etiologic agents of brucellosis, a disease affecting numerous animal species that is also a zoonotic disease for humans (4,15,17,29,39). Animal exposure most commonly occurs through inhalation, in utero exposure from infected mothers to calves, ingestion of infected fetal tissues, or in some cases may be sexually transmitted (29).…”

mentioning

confidence: 99%

Evaluation of Protection Afforded by Brucella abortus and Brucella melitensis Unmarked Deletion Mutants Exhibiting Different Rates of Clearance in BALB/c Mice

Kahl-McDonagh

Ficht

2006

Infect Immun

View full text Add to dashboard Cite

Research for novel Brucella vaccines has focused upon the development of live vaccine strains, which have proven more efficacious than killed or subunit vaccines. In an effort to develop improved vaccines, signaturetagged mutant banks were screened to identify mutants attenuated for survival. Mutants selected from these screens exhibited various degrees of attenuation characterized by the rate of clearance, ranging from a failure to grow in macrophages after 24 h of infection to a failure to persist in the mouse model beyond 8 weeks. Ideal vaccine candidates should be safe to the host, while evoking protective immunity. In the present work, we constructed unmarked deletion mutants of three gene candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella melitensis. The ⌬asp24 mutants, which persist for extended periods in vivo, are superior to current vaccine strains and to other deletion strains tested in the mouse model against homologous challenge infection after 12, 16, and 20 weeks postvaccination. The ⌬asp24 mutants also display superior protection compared to ⌬manBA and ⌬virB2 mutants against heterologous challenge in mice. From this study, a direct association between protection against infection and cytokine response was not apparent between all vaccine groups and, therefore, correlates of protective immunity will need to be considered further. A distinct correlation between persistence of the vaccine strain and protection against infection was corroborated.

show abstract

“…For pathogens, affecting the expression of cytokines, which is needed for normal protective functioning of the immune response, is one of the major strategies for surviving and multiplying in the host (21). The roles of the organism should be considered in the selective induction of the Th2 immune responses in cats.…”

Section: Discussionmentioning

confidence: 99%

Predominant T Helper 2 Immune Responses againstBartonella henselaein Naturally Infected Cats

Kabeya

Sase

Yamashita

et al. 2006

Microbiology and Immunology

View full text Add to dashboard Cite

Accumulating studies have demonstrated that Bartonella henselae is associated with a spectrum of human diseases including cat-scratch disease (CSD), bacillary angiomatosis, peliosis hepatis, endocarditis, relapsing fever and bacteremia in both immunocompetent and immunocompromised persons (6,18,25,(27)(28)(29). It has been found that bacteremic cats play an important role as a reservoir of B. henselae (5,13,22). Despite high levels of bacteria in cats for many months, most bacteremic cats are asymptomatic, and the pathogenesis and mechanisms of the establishment of persistent infection by B. henselae in cats are not fully understood (9, 17).B. henselae invades feline erythrocytes and endothelial cells, suggesting that the agent belongs to an intracellular pathogen (15). Cell-mediated immunity (CMI) is believed to play significant roles in excluding intracellular pathogens. To evaluate the functions of CMI and humoral immunity (HI), examining the cytokine expression levels in T-lymphocytes is considered important. Because it has not been possible to assess the feline cytokine expression, there has been no information about the effectiveness of CMI against B. henselae infection in cats.In the present study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the induction of feline gamma-interferon (IFN-γ) and feline interleukin 4 (IL-4), which are representatives of activations of T helper 1 (Th1) and T helper 2 (Th2), respectively. Furthermore, the mRNA expressions of tumor necrosis factor alpha (TNF-α), which is a key cytokine inducing the Th1 responses, were also examined by quantitative RT-PCR (32). The relationship between the levels of bacteremia and the Th1/Th2 cytokines were examined by using three naturally B. henselae infected cats showing relapsing bacteremia. were observed in PBMC from these infected cats after the bacteremia had peaked, showing that the T helper 2 (Th2) responses were specifically induced in the cats. Furthermore, the specific antibody titer increased, resulting in a decrease in the number of B. henselae to undetectable levels in these cats. However, the number of bacteria increased again in two of these cats at 90 and 45 days after the previous bacteremia, respectively. These results suggest that B. henselae predominantly induced IL-4 production from PBMC and resulted in stimulation of the humoral immune responses, including the secretion of specific antibodies in the cats. Furthermore, the specific antibody may play a role in eliminating the bacteria from cats partially but not completely, because relapsing bacteremia was found in these two cats. Predominant T Helper 2 Immune Responses against

show abstract

Molecular and cellular interactions between Brucella abortus antigens and host immune responses

Cited by 35 publications

References 38 publications

Pathogenesis and Immunobiology of Brucellosis

Pathogenesis and Immunobiology of Brucellosis

Evaluation of Protection Afforded by Brucella abortus and Brucella melitensis Unmarked Deletion Mutants Exhibiting Different Rates of Clearance in BALB/c Mice

Predominant T Helper 2 Immune Responses againstBartonella henselaein Naturally Infected Cats

Contact Info

Product

Resources

About