Interleukin-4 receptor-Stat6 signaling in murine infections with a tissue-dwelling nematode parasite.
Interleukin-4 (IL-4) has been shown to be crucial in parasite expulsion in several gastrointestinal nematode infection models. Data from both epidemiological studies with humans and experimental infections in animals imply a critical role for the type II helper response, dominated by IL-4, in host protection. Here we utilized inbred mice on two distinct backgrounds to document the involvement of IL-4 in the clearance of a primary infection of Brugia from the murine host. Our data from infections of IL-4 receptor(-/-) and Stat6(-/-) mice further indicate that IL-4 exerts its effects by activating the Stat6 molecule in host target cells, a finding which links clearance requirements of a gastrointestinal tract-dwelling nematode with those of a tissue-dwelling nematode. Additionally, we show that the requirements for IL-4 receptor binding and Stat6 activation extend to accelerated clearance of a secondary infection as well. The data shown here, including analysis of cell populations at the site of infection and infection of immunoglobulin E (IgE)(-/-) mice, lead us to suggest that deficiencies in eosinophil recruitment and isotype switching to IgE production may be at least partially responsible for slower parasite clearance in the absence of IL-4.
Spencer
L
L
Department of Pathology, University of Connecticut Health Center, Farmington 06030-3105, USA.
Shultz
L
L
Rajan
T V
TV
D000818:Animals; D017178:Brugia malayi; D004804:Eosinophils / Q000276:immunology; D005368:Filariasis / Q000276:immunology*; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D010529:Peritoneal Cavity / Q000469:parasitology; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D018418:Th2 Cells; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E