O papel de SIgA na resposta imune de mucosa contra ascaridiose larval

Abstract

Ascaridiosis is a chronic, globally widespread geohelmintosis that affects humans and swine. Severe morbidities associated with high parasitic loads generate impacts on public health in endemic areas. Although much of the life cycle of the parasite occurs in contact with mucous membranes (gastrointestinal and pulmonary) little is known about the role of mucosal immunity in the mechanisms that generate protection against the disease. Considering the importance of mucosal immunoglobulin-A (SIgA) in protecting against various infections, the objective of this work was to characterize the role of intestinal and pulmonary SIgA in the protection against ascaridiosis. Several immunopathological and pathophysiological parameters were evaluated in wild-type mice (BALB/c and C57BL/6j) that show different susceptibility to larval ascaridiosis (acute phase) and also in animals depleted of eosinophils or Toll-like receptors (TLR). It was also examined the use of a probiotic as an inducer of polyreactive SIgA. The results showed that both wild strains presented similar kinetic variations in the parasite load of the main organs involved in larval migration, and the difference in infection intensity among strains was just detected in hepatopulmonary migration peaks. The SIgA levels of intestinal mucosa were influenced by genetic differences, and the most resistant strain presented the highest levels of this immunoglobulin, regardless of the time evaluated. Moreover, higher levels of intestinal SIgA were associated with reduced infection intensity and less pulmonary pathology. Increases in pulmonary SIgA concentrations were induced by infection, with coincidence between SIgA peaks and pulmonary migration. In addition, positive correlations were observed between pulmonary SIgA and parasitic load. However, a coincident inversion between the kinetic curves of SIgA levels and total parasite load was identified. In animals depleted of eosinophils, TLR2 or TLR4, there was a reduction in the levels of total and specific SIgA coincident with increased parasite intensity. The use of probiotic induced increase in SIgA levels and reduction of parasitic load. Thus, the data set of this study evidenced a protective role of mucosal SIgA against murine experimental ascaridiosis, and suggesting that the efficient production of this SIgA is dependent on the activation of eosinophils and involving signaling via TLR2 and TLR4.