What have we learned from brucellosis in the mouse model?

Grilló, María-Jesús; Blasco, José María; Gorvel, Jean Pierre; Moriyón, Ignacio; Moreno, Edgardo

doi:10.1186/1297-9716-43-29

Veterinary Research

Table 2 Effect on bacterial counts in mouse spleen (CFU) after passive transfer of antibodies, cells or cytokines at different phases of smooth virulent Brucella infection

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 spleen^a		References
Treatment		Main effect in infected mice	Acute before 14 days	Chronic after 15 days	References
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	↓	↓	[84, 98, 107]
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	↓	↓	[35, 108–110]
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	[98, 112]
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	↓	↓	[27, 117]
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	↑	↑	[123, 124]
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	↑	↔	[60, 63, 124]
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]

^a (↑) Significantly higher numbers of CFU in spleen than in controls; (↓) significantly lower numbers of CFU in spleen than in controls; (↔) No significant number of CFU in spleen in relation to the controls; ND, not done.

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ISSN: 1297-9716

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