Signal Transducer and Activator of Transcription Factor 6 Signaling Contributes to Control Host Lung Pathology but Favors Susceptibility againstToxocara canisInfection

Abstract

Using STAT6−/− BALB/c mice, we have analyzed the role of STAT6-induced Th2 response in determining the outcome of experimental toxocariasis caused by embryonated eggs of the helminth parasite Toxocara canis. Following T. canis infection wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, and IL-4, recruited alternatively activated macrophages, and displayed a moderate pathology in the lungs; however, they harbored heavy parasite loads in different tissues. In contrast, similarly infected STAT6−/− BALB/c mice mounted a weak Th2-like response, did not recruit alternatively activated macrophages, displayed a severe pathology in the lungs, but efficiently controlled T. canis infection. These findings demonstrate that Th2-like response induced via STAT6-mediated signaling pathway mediates susceptibility to larval stage of T. canis. Furthermore, they also indicate that unlike most gastrointestinal helminths, immunity against larvae of T. canis is not mediated by a Th2-dominant response.

Toxocara canis mucins among other excretory-secretory antigens induce in vitro secretion of cytokines by mouse splenocytes

“…This work confirms previous observations that in the experimental model of murine toxocariasis infection induces a strong Th-2-like response with increased IL-10 and TGF-β production (Kuroda et al 2001 ; Fan et al 2004 ; Wu et al 2008 ; Faz-López et al 2013 ). We also report that despite the presence of IL-6 and TGF-β which are key cytokines in Th17 differentiation (Basso et al 2009 ), this type of immune response is not induced during T. canis infection in mice.…”

“…T. canis larvae induce strong Th2 response with IL-4 and IL-5 production (Inuo et al 1995 ; Lin et al 2008 ; Malheiro et al 2008 ; Faz-López et al 2013 ), but regulatory cytokines are also produced (Kuroda et al 2001 ; Fan et al 2004 ; Malheiro et al 2008 ). Th1 response is strongly inhibited, as production of IFN-γ and IL-12 is reduced (Kuroda et al 2001 ; Malheiro et al 2008 ).…”

A Dual Role for Macrophages in Modulating Lung Tissue Damage/Repair during L2 Toxocara canis Infection

“…Another novel finding was that the immune response in STAT6 −/− mice drove the clearance of the T. canis larvae. Previously, we reported corroborating data on parasite burden and concluded that IgE production was not essential for parasite neutralization because STAT6 −/− mice did not produce IgE [24]. A possible mechanism underlying the resistance to this parasitic infection in STAT6 −/− mice is increased activation of M1 macrophages, which favors iNOS expression.…”

“…Previously, we reported that Th2 cytokines have a dual role during toxocariasis. On the one hand, STAT6 activation contributes to host susceptibility, and, alternatively, the down-regulated immune response reduces the immunopathology induced by T. canis infection in the lungs [24].…”

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with <I>Toxocara canis</I>

“…Isolation and embryonation of eggs were performed as follows: female worms were dissected and from the uterus, eggs were isolated and placed into distilled water; then the mixture was centrifuged 2 times for 10 min at 2,000 g in a solution of NaHCl at 1%. After removal of the supernatant, the sediment was washed 2 times in distilled water and placed into the solution of 0.1 N H 2 SO 4 in tissue flasks at 28˚C for 1 month with gentle daily agitation until the end of embryonation which was controlled under the microscope [ 8 ].…”