Crucial Role of Gamma Interferon-Producing CD4<sup>+</sup>Th1 Cells but Dispensable Function of CD8<sup>+</sup>T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice

Vitry, Marie-Alice; Trez, Carl De; Goriely, Stanislas; Dumoutier, Laure; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean‐Jacques; Muraille, Eric

doi:10.1128/iai.00761-12

Cited by 87 publications

(102 citation statements)

References 74 publications

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“…In a classical i.p. infection model, we reported that IL23p19 deficiency, which is known to reduce the IL-17A production response (64), does not significantly affect the control of Brucella in the spleen but can partially compensate for IL-12p35 deficiency (16). In the present work, we observed that, following i.n.…”

Section: Discussionsupporting

confidence: 70%

“…By comparing the course of i.p. infection in the spleen in wt, IL-12p35 2/2 , IL-23p19 2/2 , and IL-12p40 2/2 (deficient for both IL-12 and IL-23) mice, we observed that IL-12p40 2/2 mice display higher susceptibility than IL-12p35 2/2 mice, which suggests a weakly compensatory role for IL-23 (affecting the IL-17A-mediated response) in the absence of IL-12p35 (affecting the IFNg-mediated response) in the spleen (16). In our i.n.…”

Section: Ifn-gr-and Il-17ra-mediated Responses Contribute To the Contmentioning

confidence: 52%

“…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. infection, and compared them with our results (16,17,35,38) obtained in the classical i.p. infection model.…”

Section: Discussionmentioning

confidence: 84%

“…As we observed previously in an i.p. model (16), the course of Brucella infection appears to be similar in the lungs, spleen, and liver of i.n. infected wt, AID 2/2 (deficient for activation-induced deaminase-mediated isotype switching), and MuMT 2/2 (deficient for B lymphocytes) C57BL/6 mice at all time points tested (Fig.…”

Section: High Mortality In Ifn-gr-deficient Mice In Response Tomentioning

confidence: 99%

“…+ T cells (15)(16)(17), and specific Abs (17) in the protective immune response against Brucella has been well established. However, those results were obtained primarily through analysis of the splenic immune response following i.p.…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 70%

Section: Ifn-gr-and Il-17ra-mediated Responses Contribute To the Contmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 84%

Section: High Mortality In Ifn-gr-deficient Mice In Response Tomentioning

confidence: 99%

mentioning

confidence: 99%

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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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Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice

Afley

Dohre

Prasad

et al. 2015

Appl Microbiol Biotechnol

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Brucellae are Gram-negative intracellular bacteria that cause an important zoonotic disease called brucellosis. The animal vaccines are available but have disadvantage of causing abortions in a proportion of pregnant animals. The animal vaccines are also pathogenic to humans. Recent trend in vaccine design has shifted to epitope-based vaccines that are safe and specific. In this study, efforts were made to identify MHC-I- and MHC-II-restricted T cell epitopes of Brucella abortus and evaluate their vaccine potential in mice. The peptides were designed using online available immunoinformatics tools, and five MHC-I- and one MHC-II-restricted T cell peptides were selected on the basis of their ability to produce interferon gamma (IFN-γ) in in vivo studies. The selected peptides were co-administered with poly DL-lactide-co-glycolide (PLG) microparticles and evaluated for immunogenicity and protection in BALB/c mice. Mice immunized with peptides either entrapped in PLG microparticles (EPLG-Pep) or adsorbed on PLG particles (APLG-Pep) showed significantly higher splenocyte proliferation and IFN-γ generation to all selected peptides than the mice immunized with corresponding irrelevant peptides formulated PLG microparticles or phosphate-buffered saline (PBS). A significant protection compared to PBS control was also observed in EPLG-Pep and APLG-Pep groups. A plasmid DNA vaccine construct (pVaxPep) for peptides encoding DNA sequences was generated and injected to mice by in vivo electroporation. Significant protection was observed (1.66 protection units) when compared with PBS and empty vector control group animals. Overall, the MHC-I and MHC-II peptides identified in this study are immunogenic and protective in mouse model and support the feasibility of peptide-based vaccine for brucellosis.

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Survey of Omp19 immunogenicity against Brucella abortus and Brucella melitensis: influence of nanoparticulation versus traditional immunization

et al. 2015

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Brucellosis is the most common zoonotic bacterial disease. Prevention of human brucellosis is achieved through pasteurization of dairy products, appropriate sanitation and vaccination of domestic animals against the Brucella species. B. abortus unlipidated 19 kDa outer membrane protein (U-Omp19) is a promising candidate for a subunit vaccine against brucellosis. This study investigates immunogenicity of Omp19 alone and with Freund's adjuvant (Omp19-IFA) and N-trimethyl chitosan (TMC/Omp19) nanoparticles, as well as the effect of Omp19 administration route on immunological responses and protection. The omp19 gene was expressed in E. coli BL21 (DE3). After purification, the recombinant Omp19 was loaded onto TMC nanoparticles by ionic gelation with tripolyphosphate. Particle size and loading efficiency of the nanoparticles were determined. Omp19-IFA was administered intraperitoneally while TMC/Omp19 nanoparticles were administered orally and intraperitoneally. The results indicated that intraperitoneal (i.p.) immunization by Omp19-IFA and TMC/Omp19 nanoparticles induced Th1 and Th2 immune responses, respectively, whereas oral immunization of TMC/Omp19 nanoparticles induced a mixed Th1/Th17 immune response. Moreover, oral immunization increased IgA levels in feces. Immunized mice were challenged with virulent B. melitensis 16 M and B. abortus 544. Oral immunization with TMC/Omp19 nanoparticles induced a remarkably high protection level against B. melitensis and B. abortus. The results showed that immunization route has a pivotal role in immune response polarization and protective efficiency of Omp19 antigen. Also, it was deduced that the higher protection level achieved through oral administration of TMC/Omp19 nanoparticles may be due to the elicited Th17 response.

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Crucial Role of Gamma Interferon-Producing CD4⁺Th1 Cells but Dispensable Function of CD8⁺T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice

Cited by 87 publications

References 74 publications

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

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

Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice

Survey of Omp19 immunogenicity against Brucella abortus and Brucella melitensis: influence of nanoparticulation versus traditional immunization

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Crucial Role of Gamma Interferon-Producing CD4+Th1 Cells but Dispensable Function of CD8+T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice

Cited by 87 publications

References 74 publications

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

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

Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice

Survey of Omp19 immunogenicity against Brucella abortus and Brucella melitensis: influence of nanoparticulation versus traditional immunization

Contact Info

Product

Resources

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Crucial Role of Gamma Interferon-Producing CD4⁺Th1 Cells but Dispensable Function of CD8⁺T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice