Interleukin-4 receptor-Stat6 signaling in murine infections with a tissue-dwelling nematode parasite.

Document Type

Article

Publication Date

2001

Keywords

Brugia-malayi, Eosinophils, Filariasis, Host-Parasite-Relations, Immunity-Natural, Immunoglobulin-Class-Switching, Immunoglobulin-E, Interleukin-4, Mice, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Mutant-Strains, Mice-SCID, Peritoneal-Cavity, Receptors-Interleukin-4, Signal-Transduction, SUPPORT-U-S-GOVT-P-H-S, Th2-Cells, Trans-Activators

First Page

7743

Last Page

7752

JAX Source

Infect Immun 2001 Dec; 69(12):7743-7752.

Grant

AI39705/AI/NIAID, AI42362/AI/NIAID

Abstract

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.

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