Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis

Journal of Immunology

Volumn 192, Issue 8, 2014, Pages 3740-3752

  Vitry, Marie Alice ^a   Mambres, Delphine Hanot ^a   De Trez, Carl ^b   Akira, Shizuo ^c   Ryffel, Bernhard ^d,e   Letesson, Jean Jacques ^a   Muraille, Eric ^f  

^a UNIVERSITY OF NAMUR   (Belgium)

^b FREE UNIVERSITY OF BRUSSELS   (Belgium)

^c OSAKA UNIVERSITY   (Japan)

^d CNRS   (France)

^e UNIVERSITY OF CAPE TOWN   (South Africa)

^f UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; ANTIBODIES, BACTERIAL; ANTIBODY SPECIFICITY; BACTEREMIA; BRUCELLA MELITENSIS; BRUCELLA VACCINE; BRUCELLOSIS; CD4-POSITIVE T-LYMPHOCYTES; H-2 ANTIGENS; IMMUNITY, HUMORAL; IMMUNOLOGIC MEMORY; INTERFERON-GAMMA; INTERLEUKIN-12; MICE; MICE, KNOCKOUT; MYELOID DIFFERENTIATION FACTOR 88; PHENOTYPE; SIGNAL TRANSDUCTION; SPLEEN; TH1 CELLS; VACCINES, INACTIVATED; VACCINES, LIVE, UNATTENUATED;

EID: 84898612244     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1302561     Document Type: Article

References (94)

1. Anderson, T. D., V. P. Meador, and N. F. Cheville. 1986. Pathogenesis of placentitis in the goat inoculated with Brucella abortus. I. Gross and histologic lesions. Vet. Pathol. 23: 219-226.
2. Enright, F. M. 1990. The Pathogenesis and Pathobiology of Brucella Infection in Domestic Animals. CRC Press, Boca Raton, FL.
3. Godfroid, J., A. Cloeckaert, J. P. Liautard, S. Kohler, D. Fretin, K. Walravens, B. Garin-Bastuji, and J. J. Letesson. 2005. From the discovery of the Malta fever's agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis. Vet. Res. 36: 313-326.
4. Colmenero, J. D., J. M. Reguera, F. Martos, D. Sánchez-De-Mora, M. Delgado, M. Causse, A. Martín-Farfán, and C. Juárez. 1996. Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore) 75: 195-211.
5. Young, E. J. 1995. An overview of human brucellosis. Clin. Infect. Dis. 21: 283-289, quiz 290.
6. Pappas, G., P. Papadimitriou, N. Akritidis, L. Christou, and E. V. Tsianos. 2006. The new global map of human brucellosis. Lancet Infect. Dis. 6: 91-99.
7. Seleem, M. N., S. M. Boyle, and N. Sriranganathan. 2010. Brucellosis: a reemerging zoonosis. Vet. Microbiol. 140: 392-398.
8. Pappas, G., P. Panagopoulou, L. Christou, and N. Akritidis. 2006. Brucella as a biological weapon. Cell. Mol. Life Sci. 63: 2229-2236.
9. Zheludkov, M. M., and L. E. Tsirel'son. 2010. Reservoirs of Brucella infection in nature. Biol. Bull. 37: 709-715.
10. Grégoire, F., B. Mousset, D. Hanrez, C. Michaux, K. Walravens, and A. Linden. 2012. A serological and bacteriological survey of brucellosis in wild boar (Sus scrofa) in Belgium. BMC Vet. Res. 8: 80.
11. Solera, J., E. Martínez-Alfaro, A. Espinosa, M. L. Castillejos, P. Geijo, and M. Rodríguez-Zapata. 1998. Multivariate model for predicting relapse in human brucellosis. J. Infect. 36: 85-92.
12. Ficht, T. A., M. M. Kahl-McDonagh, A. M. Arenas-Gamboa, and A. C. Rice-Ficht. 2009. Brucellosis: the case for live, attenuated vaccines. Vaccine 27(Suppl 4): D40-D43.
13. Oliveira, S. C., G. H. Giambartolomei, and J. Cassataro. 2011. Confronting the barriers to develop novel vaccines against brucellosis. Expert Rev. Vaccines 10: 1291-1305.
14. Arenas-Gamboa, A. M., A. C. Rice-Ficht, M. M. Kahl-McDonagh, and T. A. Ficht. 2011. Protective efficacy and safety of Brucella melitensis 16MDmucR against intraperitoneal and aerosol challenge in BALB/c mice. Infect. Immun. 79: 3653-3658.
15. Kahl-McDonagh, M. M., A. M. Arenas-Gamboa, and T. A. Ficht. 2007. Aerosol infection of BALB/c mice with Brucella melitensis and Brucella abortus and protective efficacy against aerosol challenge. Infect. Immun. 75: 4923-4932.
16. Kahl-McDonagh, M. M., and T. A. Ficht. 2006. Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of clearance in BALB/c mice. Infect. Immun. 74: 4048-4057.
17. González, D., M. J. Grilló, M. J. De Miguel, T. Ali, V. Arce-Gorvel, R. M. Delrue, R. Conde-Alvarez, P. Muñoz, I. López-Goñi, M. Iriarte, et al. 2008. Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export. PLoS ONE 3: e2760.
18. Pasquevich, K. A., S. M. Estein, C. García Samartino, A. Zwerdling, L. M. Coria, P. Barrionuevo, C. A. Fossati, G. H. Giambartolomei, and J. Cassataro. 2009. Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection. [Published erratum appears in 2009 Infect. Immun. 77: 1719.] Infect. Immun. 77: 436-445.
19. Zhan, Y., A. Kelso, and C. Cheers. 1995. Differential activation of Brucellareactive CD4+ T cells by Brucella infection or immunization with antigenic extracts. Infect. Immun. 63: 969-975.
20. Elzer, P. H., R. H. Jacobson, S. M. Jones, K. H. Nielsen, J. T. Douglas, and A. J. Winter. 1994. Antibody-mediated protection against Brucella abortus in BALB/c mice at successive periods after infection: variation between virulent strain 2308 and attenuated vaccine strain 19. Immunology 82: 651-658.
21. Araya, L. N., P. H. Elzer, G. E. Rowe, F. M. Enright, and A. J. Winter. 1989. Temporal development of protective cell-mediated and humoral immunity in BALB/c mice infected with Brucella abortus. J. Immunol. 143: 3330-3337.
22. Winter, A. J., J. R. Duncan, C. G. Santisteban, J. T. Douglas, and L. G. Adams. 1989. Capacity of passively administered antibody to prevent establishment of Brucella abortus infection in mice. Infect. Immun. 57: 3438-3444.
23. Narni-Mancinelli, E., S. M. Soudja, K. Crozat, M. Dalod, P. Gounon, F. Geissmann, and G. Lauvau. 2011. Inflammatory monocytes and neutrophils are licensed to kill during memory responses in vivo. PLoS Pathog. 7: e1002457.
24. Soudja, S. M., A. L. Ruiz, J. C. Marie, and G. Lauvau. 2012. Inflammatory Monocytes Activate Memory CD8(+) T and Innate NK Lymphocytes Independent of Cognate Antigen during Microbial Pathogen Invasion. Immunity 37: 549-562.
25. Khader, S. A., G. K. Bell, J. E. Pearl, J. J. Fountain, J. Rangel-Moreno, G. E. Cilley, F. Shen, S. M. Eaton, S. L. Gaffen, S. L. Swain, et al. 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8: 369-377.
26. Lin, L., A. S. Ibrahim, X. Xu, J. M. Farber, V. Avanesian, B. Baquir, Y. Fu, S. W. French, J. E. Edwards, Jr., and B. Spellberg. 2009. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog. 5: e1000703.
27. Schito, M. L., B. Chobotar, and J. R. Barta. 1998. Major histocompatibility complex class I-and II-deficient knock-out mice are resistant to primary but susceptible to secondary Eimeria papillata infections. Parasitol. Res. 84: 394-398.
28. Seo, S. U., H. J. Kwon, J. H. Song, Y. H. Byun, B. L. Seong, T. Kawai, S. Akira, and M. N. Kweon. 2010. MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J. Virol. 84: 12713-12722.
29. Nakayama, Y., E. H. Plisch, J. Sullivan, C. Thomas, C. J. Czuprynski, B. R. Williams, and M. Suresh. 2010. Role of PKR and Type I IFNs in viral control during primary and secondary infection. PLoS Pathog. 6: e1000966.
30. Montaraz, J. A., and A. J. Winter. 1986. Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice. Infect. Immun. 53: 245-251.
31. Zhan, Y., A. Kelso, and C. Cheers. 1993. Cytokine production in the murine response to brucella infection or immunization with antigenic extracts. Immunology 80: 458-464.
32. Huang, L., A. M. Krieg, N. Eller, and D. E. Scott. 1999. Induction and regulation of Th1-inducing cytokines by bacterial DNA, lipopolysaccharide, and heatinactivated bacteria. Infect. Immun. 67: 6257-6263.
33. Huang, L. Y., K. J. Ishii, S. Akira, J. Aliberti, and B. Golding. 2005. Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9. J. Immunol. 175: 3964-3970.
34. Huang, L. Y., J. Aliberti, C. A. Leifer, D. M. Segal, A. Sher, D. T. Golenbock, and B. Golding. 2003. Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent. J. Immunol. 171: 1441-1446.
35. Huang, L. Y., C. Reis e Sousa, Y. Itoh, J. Inman, and D. E. Scott. 2001. IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and regulation by IL-10. J. Immunol. 167: 1423-1430.
36. Montaraz, J.A., A. J. Winter, D. M.Hunter, B. A. Sowa, A. M. Wu, and L. G.Adams. 1986. Protection against Brucella abortus in mice with O-polysaccharide-specific monoclonal antibodies. Infect. Immun. 51: 961-963.
37. Araya, L. N., and A. J. Winter. 1990. Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum. Infect. Immun. 58: 254-256.
38. Grilló, M. J., J. M. Blasco, J. P. Gorvel, I. Moriyón, and E. Moreno. 2012. What have we learned from brucellosis in the mouse model? Vet. Res. 43: 29.
39. Kawai, T., O. Adachi, T. Ogawa, K. Takeda, and S. Akira. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115-122.
40. Mattner, F., J. Magram, J. Ferrante, P. Launois, K. Di Padova, R. Behin, M. K. Gately, J. A. Louis, and G. Alber. 1996. Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response. Eur. J. Immunol. 26: 1553-1559.
41. Muramatsu, M., K. Kinoshita, S. Fagarasan, S. Yamada, Y. Shinkai, and T. Honjo. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553-563.
42. Cosgrove, D., D. Gray, A. Dierich, J. Kaufman, M. Lemeur, C. Benoist, and D. Mathis. 1991. Mice lacking MHC class II molecules. Cell 66: 1051-1066.
43. Mombaerts, P., J. Iacomini, R. S. Johnson, K. Herrup, S. Tonegawa, and V. E. Papaioannou. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68: 869-877.
44. Stamm, L. M., A. Räisänen-Sokolowski, M. Okano, M. E. Russell, J. R. David, and A. R. Satoskar. 1998. Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis. J. Immunol. 161: 6180-6188.
45. Kitamura, D., J. Roes, R. Kühn, and K. Rajewsky. 1991. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350: 423-426.
46. Copin, R., P. De Baetselier, Y. Carlier, J. J. Letesson, and E. Muraille. 2007. MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J. Immunol. 178: 5182-5191.
47. Shaner, N. C., R. E. Campbell, P. A. Steinbach, B. N. Giepmans, A. E. Palmer, and R. Y. Tsien. 2004. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22: 1567-1572.
48. Köhler, S., S. Ouahrani-Bettache, M. Layssac, J. Teyssier, and J. P. Liautard. 1999. Constitutive and inducible expression of green fluorescent protein in Brucella suis. Infect. Immun. 67: 6695-6697.
49. Copin, R., M. A. Vitry, D. Hanot Mambres, A. Machelart, C. De Trez, J. M. Vanderwinden, S. Magez, S. Akira, B. Ryffel, Y. Carlier, et al. 2012. In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice. PLoS Pathog. 8: e1002575.
50. Sathiyaseelan, J., R. Goenka, M. Parent, R. M. Benson, E. A. Murphy, D. M. Fernandes, A. S. Foulkes, and C. L. Baldwin. 2006. Treatment of Brucella-susceptible mice with IL-12 increases primary and secondary immunity. Cell. Immunol. 243: 1-9.
51. Lang, R., B. Shasha, and E. Rubinstein. 1993. Therapy of experimental murine brucellosis with streptomycin alone and in combination with ciprofloxacin, doxycycline, and rifampin. Antimicrob. Agents Chemother. 37: 2333-2336.
52. Fernandes, D. M., X. Jiang, J. H. Jung, and C. L. Baldwin. 1996. Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308. FEMS Immunol. Med. Microbiol. 16: 193-203.
53. Baldwin, C. L., and M. Parent. 2002. Fundamentals of host immune response against Brucella abortus: what the mouse model has revealed about control of infection. Vet. Microbiol. 90: 367-382.
54. Zhan, Y., and C. Cheers. 1995. Differential induction of macrophage-derived cytokines by live and dead intracellular bacteria in vitro. Infect. Immun. 63: 720-723.
55. Vitry, M. A., C. De Trez, S. Goriely, L. Dumoutier, S. Akira, B. Ryffel, Y. Carlier, J. J. Letesson, and E. Muraille. 2012. 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. Infect. Immun. 80: 4271-4280.
56. Goenka, R., M. A. Parent, P. H. Elzer, and C. L. Baldwin. 2011. B cell-deficient mice display markedly enhanced resistance to the intracellular bacterium Brucella abortus. J. Infect. Dis. 203: 1136-1146.
57. Murphy, E. A., J. Sathiyaseelan, M. A. Parent, B. Zou, and C. L. Baldwin. 2001. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology 103: 511-518.
58. Stevens, M. G., G. W. Pugh, Jr., and L. B. Tabatabai. 1992. Effects of gamma interferon and indomethacin in preventing Brucella abortus infections in mice. Infect. Immun. 60: 4407-4409.
59. Zhan, Y., and C. Cheers. 1993. Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect. Immun. 61: 4899-4901.
60. Ko, J., A. Gendron-Fitzpatrick, and G. A. Splitter. 2002. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. J. Immunol. 168: 2433-2440.
61. Martirosyan, A., E. Moreno, and J. P. Gorvel. 2011. An evolutionary strategy for a stealthy intracellular Brucella pathogen. Immunol. Rev. 240: 211-234.
62. Cutler, S. J., A. M. Whatmore, and N. J. Commander. 2005. Brucellosis-new aspects of an old disease. J. Appl. Microbiol. 98: 1270-1281.
63. Ariza, J., J. Corredoira, R. Pallares, P. F. Viladrich, G. Rufi, M. Pujol, and F. Gudiol. 1995. Characteristics of and risk factors for relapse of brucellosis in humans. Clin. Infect. Dis. 20: 1241-1249.
64. Perkins, S. D., S. J. Smither, and H. S. Atkins. 2010. Towards a Brucella vaccine for humans. FEMS Microbiol. Rev. 34: 379-394.
65. Durward, M., G. Radhakrishnan, J. Harms, C. Bareiss, D. Magnani, and G. A. Splitter. 2012. Active evasion of CTL mediated killing and low quality responding CD8+ T cells contribute to persistence of brucellosis. PLoS ONE 7: e34925.
66. Chakravortty, D., and M. Hensel. 2003. Inducible nitric oxide synthase and control of intracellular bacterial pathogens. Microbes Infect. 5: 621-627.
67. Casadevall, A., and L. A. Pirofski. 2006. A reappraisal of humoral immunity based on mechanisms of antibody-mediated protection against intracellular pathogens. Adv. Immunol. 91: 1-44.
68. Kima, P. E., S. L. Constant, L. Hannum, M. Colmenares, K. S. Lee, A. M. Haberman, M. J. Shlomchik, and D. McMahon-Pratt. 2000. Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. J. Exp. Med. 191: 1063-1068.
69. Buxbaum, L. U., and P. Scott. 2005. Interleukin 10-and Fcgamma receptordeficient mice resolve Leishmania mexicana lesions. Infect. Immun. 73: 2101-2108.
70. Padigel, U. M., and J. P. Farrell. 2005. Control of infection with Leishmania major in susceptible BALB/c mice lacking the common gamma-chain for FcR is associated with reduced production of IL-10 and TGF-beta by parasitized cells. J. Immunol. 174: 6340-6345.
71. Bitsaktsis, C., B. Nandi, R. Racine, K. C. MacNamara, and G. Winslow. 2007. T-Cell-independent humoral immunity is sufficient for protection against fatal intracellular ehrlichia infection. Infect. Immun. 75: 4933-4941.
72. Goenka, R., P. D. Guirnalda, S. J. Black, and C. L. Baldwin. 2012. B Lymphocytes provide an infection niche for intracellular bacterium Brucella abortus. J. Infect. Dis. 206: 91-98.
73. Racine, R., and G. M. Winslow. 2009. IgM in microbial infections: taken for granted? Immunol. Lett. 125: 79-85.
74. Alugupalli, K. R., J. M. Leong, R. T. Woodland, M. Muramatsu, T. Honjo, and R. M. Gerstein. 2004. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity 21: 379-390.
75. Racine, R., M. McLaughlin, D. D. Jones, S. T. Wittmer, K. C. MacNamara, D. L. Woodland, and G. M. Winslow. 2011. IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection. J. Immunol. 186: 1011-1021.
76. Defrance, T., M. Taillardet, and L. Genestier. 2011. T cell-independent B cell memory. Curr. Opin. Immunol. 23: 330-336.
77. Ko, J., A. Gendron-Fitzpatrick, T. A. Ficht, and G. A. Splitter. 2002. Virulence criteria for Brucella abortus strains as determined by interferon regulatory factor 1-deficient mice. Infect. Immun. 70: 7004-7012.
78. Izadjoo, M. J., Y. Polotsky, M. G. Mense, A. K. Bhattacharjee, C. M. Paranavitana, T. L. Hadfield, and D. L. Hoover. 2000. Impaired control of Brucella melitensis infection in Rag1-deficient mice. Infect. Immun. 68: 5314-5320.
79. Finkelman, F. D., I. M. Katona, T. R. Mosmann, and R. L. Coffman. 1988. IFNgamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J. Immunol. 140: 1022-1027.
80. He, Y., R. Vemulapalli, A. Zeytun, and G. G. Schurig. 2001. Induction of specific cytotoxic lymphocytes in mice vaccinated with Brucella abortus RB51. Infect. Immun. 69: 5502-5508.
81. Muñoz-Montesino, C., E. Andrews, R. Rivers, A. González- Smith, G. Moraga-Cid, H. Folch, S. Céspedes, and A. A. Oñate. 2004. Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells. Infect. Immun. 72: 2081-2087.
82. Cassataro, J., C. A. Velikovsky, S. de la Barrera, S. M. Estein, L. Bruno, R. Bowden, K. A. Pasquevich, C. A. Fossati, and G. H. Giambartolomei. 2005. A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infect. Immun. 73: 6537-6546.
83. Yu, D. H., X. D. Hu, and H. Cai. 2007. A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses. DNA Cell Biol. 26: 435-443.
84. Durward, M. A., J. Harms, D. M. Magnani, L. Eskra, and G. A. Splitter. 2010. Discordant Brucella melitensis antigens yield cognate CD8+ T cells in vivo. Infect. Immun. 78: 168-176.
85. Cassataro, J., S. M. Estein, K. A. Pasquevich, C. A. Velikovsky, S. de la Barrera, R. Bowden, C. A. Fossati, and G. H. Giambartolomei. 2005. Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infect. Immun. 73: 8079-8088.
86. Oliveira, S. C., J. S. Harms, M. Banai, and G. A. Splitter. 1996. Recombinant Brucella abortus proteins that induce proliferation and gamma-interferon secretion by CD4+ T cells from Brucella-vaccinated mice and delayed-type hypersensitivity in sensitized guinea pigs. Cell. Immunol. 172: 262-268.
87. Goldsack, L., and J. R. Kirman. 2007. Half-truths and selective memory: Interferon gamma, CD4(+) T cells and protective memory against tuberculosis. Tuberculosis (Edinb.) 87: 465-473.
88. Gallegos, A. M., J. W. van Heijst, M. Samstein, X. Su, E. G. Pamer, and M. S. Glickman. 2011. A gamma interferon independent mechanism of CD4 T cell mediated control of M. tuberculosis infection in vivo. PLoS Pathog. 7: e1002052.
89. Mittrücker, H. W., U. Steinhoff, A. Köhler, M. Krause, D. Lazar, P. Mex, D. Miekley, and S. H. Kaufmann. 2007. Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis. Proc. Natl. Acad. Sci. USA 104: 12434-12439.
90. Cowley, S. C., and K. L. Elkins. 2003. CD4+ T cells mediate IFN-γammaindependent control of Mycobacterium tuberculosis infection both in vitro and in vivo. J. Immunol. 171: 4689-4699.
91. Brandäo, A. P., F. S. Oliveira, N. B. Carvalho, L. Q. Vieira, V. Azevedo, G. C. Macedo, and S. C. Oliveira. 2012. Host susceptibility to Brucella abortus infection is more pronounced in IFN-γ knockout than IL-12/b2-microglobulin double-deficient mice. Clin. Dev. Immunol. 2012: 589494.
92. Narni-Mancinelli, E., L. Campisi, D. Bassand, J. Cazareth, P. Gounon, N. Glaichenhaus, and G. Lauvau. 2007. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J. Exp. Med. 204: 2075-2087.
93. Suraud, V., I. Jacques, M. Olivier, and L. A. Guilloteau. 2008. Acute infection by conjunctival route with Brucella melitensis induces IgG+ cells and IFN-γamma producing cells in peripheral and mucosal lymph nodes in sheep. Microbes Infect. 10: 1370-1378.
94. Magnani, D. M., J. S. Harms, M. A. Durward, and G. A. Splitter. 2009. Nondividing but metabolically active gamma-irradiated Brucella melitensis is protective against virulent B. melitensis challenge in mice. Infect. Immun. 77: 5181-5189. Médicale