pcDNA-IL-12 vaccination blocks eosinophilic inflammation but not airway hyperresponsiveness following murine Toxocara canis infection.
We have investigated the effect of pcDNA3-CpG and pcDNA-IL-12, delivered by intradermal gene gun administration, on the blood/lung eosinophilia, airway hyperresponsiveness as well as the immune response in a murine model of toxocariasis. Our results demonstrated that pcDNA-IL-12 but not pcDNA3-CpG vaccination led to a persistent lower blood/bronchoalveolar eosinophilia following Toxocara canis infection, as pcDNA3-CpG led only to an early transient blockage of eosinophil transmigration into bronchoalveolar fluid following T. canis infection. Prominent Type-1 immune response was pointed out as the hallmark of T. canis infection following pcDNA-IL-12 vaccination. Outstanding IFN-gamma/IL-4 ratio besides low levels of IgG1 with subsequent high IgG2a/IgG1 ratio further characterized a Type-1 polarized immunological profile in pcDNA-IL-12-vaccinated animals. Nevertheless, only pcDNA3-CpG was able to prevent airway hyperresponsiveness induced by T. canis infection. The persistent airway hyperresponsiveness observed in pcDNA-IL-12-vaccinated animals demonstrated that the airway constriction involved other immunological mediator than those blocked by pcDNA-IL-12. Together, these data indicated that pcDNA-IL-12 and pcDNA3-CpG vaccines have distinct therapeutic benefits regarding the eosinophilic inflammation/airway hyperresponsiveness triggered by T. canis infection, suggesting their possible use in further combined therapeutic interventions.
Malheiro
Adriana
A
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. malheiroadriana@yahoo.com.br
Aníbal
Fernanda F
FF
Martins-Filho
Olindo Assis
OA
Teixeira-Carvalho
Andréa
A
Perini
Adenir
A
Martins
Milton A
MA
Medeiros
Alexandra I
AI
Turato
Walter M
WM
Acencio
Milene P M
MP
Brandão
Izaíra T
IT
Nomizo
Auro
A
Silva
Célio L
CL
Faccioli
Lúcia H
LH
D000818:Animals; D019470:Biolistics; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology; D004285:Dogs; D005260:Female; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D011657:Pulmonary Eosinophilia / Q000517:prevention & control*; D017166:Toxocara canis; D014120:Toxocariasis / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D016896:Treatment Outcome; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D019444:Vaccines, DNA; D018664:Interleukin-12