Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis.
Infection usually leads to the development of acquired immune responses associated with clearance or control of the infecting organism. However, if not adequately regulated, immune-mediated pathology can result. Tuberculosis is a worldwide threat, and development of an effective vaccine requires that the protective immune response to Mycobacterium tuberculosis (Mtb) be dissected from the pathological immune response. This distinction is particularly important if new vaccines are to be delivered to Mtb-exposed individuals, as repeated antigenic exposure can lead to pathological complications. Using a model wherein mice are vaccinated with bacille Calmette-Guérin after Mtb infection, we show that repeated vaccination results in increased IL-17, tumor necrosis factor, IL-6, and MIP-2 expression, influx of granulocytes/neutrophils, and lung tissue damage. This pathological response is abrogated in mice deficient in the gene encoding IL-23p19 or in the presence of IL-17-blocking antibody. This finding that repeated exposure to mycobacterial antigen promotes enhanced IL-17-dependent pathological consequences has important implications for the design of effective vaccines against Mtb.
Cruz
Andrea
A
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.
Fraga
Alexandra G
AG
Fountain
Jeffrey J
JJ
Rangel-Moreno
Javier
J
Torrado
Egídio
E
Saraiva
Margarida
M
Pereira
Daniela R
DR
Randall
Troy D
TD
Pedrosa
Jorge
J
Cooper
Andrea M
AM
Castro
António G
AG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001500:BCG Vaccine / Q000009:adverse effects* / Q000276:immunology*; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054426:Chemokine CXCL2 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006099:Granuloma / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014611:Vaccination
D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D054426:Chemokine CXCL2; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C551746:granulocyte receptor 1, mouse; D007371:Interferon-gamma