Infection withStrongyloides venezuelensisInduces Transient Airway Eosinophilic Inflammation, an Increase in Immunoglobulin E, and Hyperresponsiveness in Rats

Abstract

Infection by nematode parasites with a pulmonary migration in their life cycle and allergic asthma are two highly prevalent diseases in humans; therefore, one may expect both may occur concomitantly. There is a predominant and essential role of Th2 lymphocytes in the mechanisms underlying the control of parasite elimination as well as in the pathology observed in the asthmatic lung. The consequences of such situations have been explored, with controversial results, justifying the development of experimental models in which the relationship between allergic airway inflammation and helminth infection might be evaluated. The present work describes the inflammatory, humoral, and functional changes that occur in the lung of rats after single (subcutaneous inoculation of 1,500 L3 larvae) or multiple (five weekly subcutaneous inoculations of 1,500 L3 larvae) Strongyloides venezuelensis infections. The results show that the migration of S. venezuelensis larvae through the lungs of infected rats induces a local eosinophilic inflammation process which is mostly focal and parenchymal for rats infected a single time and which is peribronchial after multiple infections. The inflammatory process is accompanied by mucus hypersecretion, thickening of bronchial epithelial and muscle layers, and local increase in immunoglobulin E concentrations that peak after 5 to 7 days and are resolved after 12 days of single or multiple infections. The peak of lung immunopathologic changes observed in infected rats coincides with lung airway hyperresponsiveness (AHR), a key functional alteration in asthma. We propose that this experimental model is ideal to carry out further studies on immunoprotection against nematode infection versus immunopathology of allergic airway inflammation.

Platelet-Activating Factor Receptor Deficiency Delays Elimination of Adult Worms but Reduces Fecundity inStrongyloides venezuelensis-Infected Mice

“…In addition, several experiments have linked PAF to allergic processes (25; reviewed in reference 21). It has been demonstrated previously that S. venezuelensis infection induces eosinophilic lung inflammation that is accompanied by airway hyperreactivity in rats (37,50). A similar inflammatory reaction is observed in the small intestine of Strongyloides-infected mice (15,24,32).…”

“…In experimental infections, S. venezuelensis larvae have an obligatory migration through the lungs of the host before they become established in the duodenal mucosa (52), similar to the migration of S. stercoralis in humans, and the adult worms are spontaneously eliminated after 5 weeks in rats (55) and after 10 to 14 days of infection in mice (46). The migration of parasite larvae (37,50) or establishment of the worm in the gut (24,26) results in eosinophilic inflammation. Moreover, arrival of the parasite in the intestine is accompanied by intestinal eosinophilia and mastocytosis, which may be associated with the process of worm elimination (10,24,26).…”

“…One experimental model that has been used to study the aspects of immunoprotection and immunoregulation during gastrointestinal infection is infection of rodents with Strongyloides venezuelensis (29,30,40,50), a nematode that naturally infects wild rats. In experimental infections, S. venezuelensis larvae have an obligatory migration through the lungs of the host before they become established in the duodenal mucosa (52), similar to the migration of S. stercoralis in humans, and the adult worms are spontaneously eliminated after 5 weeks in rats (55) and after 10 to 14 days of infection in mice (46).…”

“…The EPO assay, performed as described by Silveira et al (50), was used to estimate the numbers of eosinophils in the lungs and intestine.…”

Contribution of IL-33–activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice

“…Because helminth infection strongly induces Th2 immune response (4), it is generally accepted that Th2 cells are responsible for inducing both systemic eosinophilia and local pulmonary eosinophilia (Löffler syndrome) (34). On the other hand, it is well documented that most of the nematodes cause pulmonary eosinophilia during larval migration through the lungs (35,36). Indeed, we observed several hemorrhagic areas in the lung tissues of mice at day 5 after S. venezuelensis infection.…”