Counterregulation of Th2 immunity by interleukin 12 reduces host defenses against Strongyloides venezuelensis infection

Abstract

The aim of this study was to investigate the role of interleukin 12 (IL-12) during Strongyloides venezuelensis infection. IL-12(-/-) and wild-type C57BL/6 mice were subcutaneously infected with 1500 larvae of S. venezuelensis. On days 7, 14, and 21 post-infection, we determined eosinophil and mononuclear cell numbers in the blood and broncoalveolar lavage fluid (BALF), Th2 cytokine secretion in the lung parenchyma, and serum antibody levels. The numbers of eggs in the feces and worm parasites in the duodena were also quantified. The eosinophil and mononuclear cell counts and the concentrations of IL-3, IL-5, IL-10, IL-13, and IgG1 and IgE antibodies increased significantly in infected IL-12(-/-) and wild-type mice as compared with uninfected controls. However, the number of eosinophils and mononuclear cells in the blood and BALF and the Th2 cytokine levels in the lungs of infected IL-12(-/-) mice were greater than in infected wild-type C57BL/6 mice. In addition, serum IgE and IgG1 levels were also significantly enhanced in the infected mice lacking IL-12. Meanwhile, parasite burden and fecal egg counts were significantly decreased in infected IL-12(-/-) mice. Together, our results showed that the absence of IL-12 upregulates the Th2 immune response, which is important for control of S. venezuelensis infection.

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

“…Our combined findings strongly suggested that this improved expulsion of parasitic adults was mediated by the increased and accelerated mast cell activation observed in the absence of Tregs, because activated mast cells were shown to be the major cell type responsible for parasite expulsion, especially in murine Strongyloides infections (32,34,50). This increased mast cell activation again was very likely a direct consequence of the increased Th2 response also observed upon Treg depletion, because the initiation of a potent Th2 response is central for the timely expulsion of Strongyloides adults (36,51). However, it is also conceivable that Tregs suppressed mast cells directly by cellular interaction via OX40, as was shown recently (52).…”

Cutting Edge: The BTLA–HVEM Regulatory Pathway Interferes with Protective Immunity to Intestinal Helminth Infection

“…Control of Strongyloides infection in the intestine was shown to depend on a functional Th2 response (14,15) and activated mast cells (16). To analyze the immunological mechanism that reduced parasite burden in BTLA 2/2 and HVEM 2/2 mice, we quantified the cytokine response during S. ratti infection (Fig.…”

Hyperinfection Syndrome in Strongyloidiasis

“…Several immunoglobulins, such as IgE, IgG and IgM, are essential for the elimination of the parasite (Ligas et al, 2003;Machado et al, 2005). IgE antibodies can mediate the activation of accessory cells and the recognition of parasite antigens, promoting goblet cell mucus secretion and the degranulation of mast cells that release mediators affecting parasite survival (Machado et al, 2009). IgG and IgM can transfer immunity against the human parasite in the presence of the complement system and neutrophils (Abraham et al, 1995;Vadlamudi et al, 2006) Laboratory models have suggested that both T and B cells mediate the immune response through an increase in immunoglobulins, eosinophils and mast cells and hyperplasia of goblet cells, which require interleukins and chemokines for their development and activation.…”