Blocking the receptor for IL-10 improves antimycobacterial chemotherapy and vaccination.
Novel approaches are required for the prevention and therapy of mycobacterial infections since the only vaccine in use, bacillus Calmette-Guérin, is poorly effective and chemotherapy is long and often ineffective in sterilizing the infection. We used a mouse model of Mycobacterium avium infection to address the usefulness of a mAb able to block IL-10R both in treatment of primary infections and in conventional multidrug therapy and subunit vaccination. Treatment of infected mice with this mAb during the entire period of experimental infection had little impact on the course of M. avium infection, with a slight improvement in the resistance of infected mice observed in the liver and spleen at day 30 of infection, which was associated with increased macrophage activation and priming of CD4(+) T cells for IFN-gamma production. Administration of this mAb later in infection had no effect on its course, but improved the effectiveness of chemotherapy when the latter was started in a chronic phase of infection. Also, the anti-IL-10R mAb acted as an adjuvant in the induction of protective immunity upon vaccination with a mycobacterial subunit preparation.
Silva
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Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Rua do Casmpo Alegre 823, 4150-180 Porto, Portugal.
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Appelberg
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004357:Drug Synergism; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000276:immunology; D053701:Receptors, Interleukin-10
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000995:Antitubercular Agents; D001428:Bacterial Vaccines; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10