From: What have we learned from brucellosis in the mouse model?
Treatment | Administration of treatment in relation to the time of infection | Main effect in infected mice | Brucella CFU in the spleena | References | |
---|---|---|---|---|---|
Acute before 14 days | Chronic after 15 days | ||||
Rabbit anti-Brucella | 2 h, 16 h before or 2 h after | Immune serum from Brucella infected mice directed against a variety of different antigens | ↓ | ↓ | [106] |
Murine anti-Brucella | 2 h, 16 h before or 2 h after | Immune serum from Brucella infected mice directed against a variety of different antigens | ↓ | ↓ | |
Anti-LPS | 16 h before | Immune murine sera against Brucella LPS | ↓ | ↓ | [84] |
Anti-O:9 | 16 h before | Immune murine sera against Yersinia enterocolitica O:9. It protects mice but to a lesser extent than anti-Brucella | ↓ | ↓ | [84] |
Anti-peptido-glycan | 16 h before | Polyclonal immune sera against peptidoglycan protein complex, probably contaminated with LPS | ↓ | ↓ | [84] |
Mabs anti-O- chain LPS | 4 h before | Several antibody isotypes reacting against A, M and C epitopes of the B. abortus O chain of LPS | ↓ | ↓ | |
Mabs anti-Omps | 24 h before | Against Omps of molecular weight 10, 16.5, 19, 25–27, 31–34, 36–38 and 89 | ↔ | ↔ | [109] |
Mab-anti-Omp16 | 24 h before | It induces lower protection than anti- O chain antibodies; IgG2a isotype | ↓ | ND | [109] |
Mab-anti-Omp25 | 24 h before | It induces lower protection than anti-O chain antibodies; IgG2a isotype | ↓ | ND | [109] |
Mab-anti-Omp2b | 4 h before | Reacts against B. abortus Omp2b, which generally is not accessible in smooth bacteria | ↔ | ND | [35] |
Mab-anti-Omp31 | 24 h before | It induces lower protection than anti-O chain LPS antibodies; IgG2a isotype | ↓ | ND | [109] |
Spleen cells | Same day as infection | Protection was efficiently transferred to naive mice using spleen cells from mice infected 5 or 12 weeks earlier | ND | ↓ | [111] |
Immune Tcells | 2 h after infection | It gave similar protection than CD8+ or CD4+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection. | ↓ | ND | |
Immune CD4+T cells | 2 h after infection | It gave similar protection than CD8+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection | ↓ | ND | [107] |
Immune CD8+T cells | 2 h after infection | It gave similar protection than CD4+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection | ↓ | ND | [107] |
Serum anti-Brucella and T cells | 2 h after infection | Enhanced protection over administration of just T cells or Abs alone | ↓ | ND | [107] |
Immune T cell+anti- INF-γ | Anti- INF-γ 1day before T cells with challenge | It gave similar protection than passively transferred T cells | ↔ | ND | [112] |
Bovine Mø | 1 day before infection | Transferred to NK1.1 cell-depleted Rag-1−/− mice | ↔ | ND | [60] |
Bovine Mø+γδT cells | 1 day before infection | Transferred to NK1.1 cell-depleted Rag-1−/− mice | ↓ | ND | [60] |
Bovine Mø+CD4 T cells | 1 day before infection | Transferred to NK1.1 cell-depleted Rag-1−/− mice | ↔ | ND | [60] |
INF-γ | 1 day before and 2 and 4 day after | It Induces splenomegaly. Mice show enhanced peritoneal and splenic macrophage bactericidal activity | ↓ | ND | [113] |
IL-12 | With the infection and every 3 days after | The levels of INF-γ increase during the third week of infection | ↔ | ↓ | [114] |
IL-1α | 4 h before | CSF-1 increases in serum during the first 12 h. Colony forming cells increase in the spleen, mainly Mø and PMNs. Thirty days after treatment, the effect is terminated. | ↓ | ↓ | [28] |
Transfer factor | At the sametime | No effect in immune enhancement or antibody response | ND | ↔ | [115] |
Indomethacin | Daily s. c. for 7 days | Decrease of the cyclooxygenase activity by 80 to 90 % in spleen. Reduction of PGE2 | ↓ | ND | [113] |
Poly A:U | 2 h before and 2, 4, and 6 days after | Activation of NK cell activity | ↔ | ND | [116] |
Poly A:U | At the sametime | Polyadenylic acid-polyuridylic acid (poly A: U) is a non-toxic adjuvant that potentiates both humoral and cell-mediated immune responses | ↓ | ↓ | |
Cyclosporine | Daily for 4 weeks | It induces low inflammatory response in spleen and liver. No significant changes in spleen macrophage population | ND | ↑ | [107] |
Corticosteroids | 24 h before | It has a broad anti-inflammatory effects | ↑ | ↑ | [3] |
Anti-Ia | 24 h before | It depletes mostly B cells and some T cell subpopulation with “suppressor” activity | ND | ↔ | [111] |
Anti-CD8+ T cells | 5 days before and 3 per week | Depletion of CD8+ cells. DTH response was unaffected after treatment. Treatment abolished the IgG antibody response without affecting bacterial numbers. | ND | ↑ | [111] |
Anti-CD8+ T cells | 1 day before and every 4 days after | Depletion of CD8+ cells, significant increase of Møs in spleen. No significant effect in the number of CD4+, NK or γδ T cells | ND | ↑ | [118] |
Anti-CD8+ | 1 day before and every 3 days after | Depletion of CD8+ lymphocytes involved in cell mediated cytotoxicity of infected cells | ND | ↔ | [119] |
Anti-CD8+ | 2 days before and 1,4,7 10 days after | Depletion of CD8+ lymphocytes involved in cell mediated cytotoxicity of infected cells | ND | ↑ | [56] |
Anti-CD4+ | 2 days before and 1,4,7 10 days after | Influences the Th1 profile mainly INF-γ. It induces basal levels of IL2 and IL4 | ND | ↓ | [56] |
Anti-CD4+ | Reduces granulomatous inflammation, which seems to be mediated mainly by CD4+ T cells | ND | ↔ | [119] | |
Anti-CD25+ T cells | 3 days before | Depletion of CD4+ regulatory T cells. Increase levels of INF-γ in spleen cells | ND | ↓ | [120] |
Anti-NK1.1cells | 24 h before | Depletion of NK cells and activity | ↔ | ND | [116] |
Anti-asialo-GM1 | 24 h before and 3 day after | Depletion of NK cells and activity | ↔ | ND | [116] |
Anti-PMN-RB6 | 24 h before and3, 6, 9 days after | It depletes neutrophils and a small population of Møs. It does not affect the course of brucellosis. In some cases CFU decrease in numbers after 9 days of treatment | ↔/↓ | ND | [48],unpublished results] |
Anti-IL-10 | 1 day before and 4 days after | The levels of INF-γ increase during the first week of infection | ↓ | ND | [121] |
Anti-IL-10 | 1 day before and 4 days after | Augments the production of INF-γ in spleen cells of both, sensitive and resistant mouse strains | ↓ | ND | [122] |
Anti-IL-12 | 4 h before, or 2 days after, or 7 days after | Decrease in spleen weight and spleen inflammation in relation to infected non-treated mice. There is granuloma reduction and low levels of INF-γ | ↑ | ↑ | |
Anti-IL-4 | 24 h before and 4 days after | Removal of IL-4 It depresses the Th2 Ab response and indirectly may favor the Th1 response | ↓ | ND | [122] |
Anti-INF-γ | 1 day before infection | Reduces splenomegaly | ↑ | ND | [112] |
Anti-INF-γ | 1 day before and every 5 days after | No significant effect was observed even after administration with IL-12 | ND | ↔ | [114] |
Anti-INF-γ | 1 day before and 4 days after | It removes secreted INF-γ and depressed Th1 response | ↑ | ND | [121] |
Anti-INF-γ | 24 h before and 4 days after | It removes secreted INF-γ and depressed Th1 response | ↑ | ND | [122] |
Anti-TNF-α | 1 day before and every 4 days after | No significant effect in the number of PMNs, CD4, CD8, NK, γδ T cells or Møs is observed | ND | ↑ | [118] |
Anti-TNF-α | 4 h before, or 2 days after, or 7 days after | Decrease in spleen weight and spleen inflammation with respect to the infected non-treated mice. INF-γ is detected at normal levels | ↑ | ↔ | |
Anti-TCRγδ | The same day and 3 days after | Removes Tγδ cells if innate immunity. Depletion has similar effect in IL/17Rα KO, INF-γ KO and GM-CSF KO mice | ↑ | ND | [60] |