Persistent airway hyper-responsiveness and inflammation in Toxocara canis-infected BALB/c mice.
BACKGROUND
Infection with Toxocara canis, the roundworm of dogs, has been associated with asthmatic manifestations. Clinical symptoms such as wheezing, coughing and episodic airflow obstruction have been described for patients infected with this helminth.


OBJECTIVE
In order to characterize the effect of T. canis infection on the lungs, we monitored immune responses, pulmonary pathology and lung function over a period of 60 days in BALB/c mice.


METHODS
Infection was performed by a single oral administration of 1000 T. canis embryonated eggs. Airway responsiveness was measured in conscious, unrestrained mice at 7, 14, 30 and 60 days post-infection (p.i.).


RESULTS
Infection of mice resulted in airway hyper-responsiveness (AHR) that persisted up to 30 days p.i. Pulmonary inflammation as well as increased levels of IgE and eosinophils in bronchoalveolar lavage (BAL) persisted up to 60 days p.i. Cytokine analysis in BAL indicated increased levels of IL-5 at day 7 and 14 p.i., whereas the levels of IL-2, IFN-gamma, IL-4 and IL-10 did not differ from those of uninfected controls. Toxocara-specific stimulation of spleen cells using recombinant TES-70 protein resulted in the induction of IL-5 at day 7 and 14 p.i. and IL-10 at day 14 p.i. Production of all other cytokines did not differ from that of uninfected controls. Evaluation of larval burden revealed that T. canis was still present in the lungs of infected mice at 60 days p.i.


CONCLUSIONS
The presence of Toxocara larva in the lungs at 60 days p.i. following a single infection could explain the persistent pulmonary inflammation, airway hyper-reactivity, eosinophilia and increased IgE production observed in T. canis-infected BALB/c mice.
Pinelli
E
E
Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. elena.pinelli@rivm.nl
Withagen
C
C
Fonville
M
M
Verlaan
A
A
Dormans
J
J
van Loveren
H
H
Nicoll
G
G
Maizels
R M
RM
van der Giessen
J
J
D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004285:Dogs; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008174:Lung Diseases, Parasitic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010270:Parasite Egg Count / Q000379:methods; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D017166:Toxocara canis / Q000276:immunology*; D014120:Toxocariasis / Q000150:complications / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D007073:Immunoglobulin E