IL-4 is required to prevent filarial nematode development in resistant but not susceptible strains of mice.
The murine Litomosoides sigmodontis model of filarial infection provides the opportunity to elucidate the immunological mechanisms that determine whether these nematode parasites can establish a successful infection or are rejected by the mammalian host. BALB/c mice are fully susceptible to L. sigmodontis infection and can develop patent infection, with the microfilarial stage circulating in the bloodstream. In contrast, mice on the C57BL background are largely resistant to the infection and never produce a patent infection. In this study, we used IL-4 deficient mice on the C57BL/6 background to address the role of IL-4 in the development of L. sigmodontis parasites in a resistant host. Two months after infection, adult worm recovery and the percentage of microfilaraemic mice in infected IL-4 deficient mice were comparable with those of the susceptible BALB/c mice while, as expected, healthy adults were not recovered from wild type C57BL/6 mice. The cytokine and antibody responses reveal that despite similar parasitology the two susceptible strains (BALB/c and IL-4 deficient C57BL/6) have markedly different immune responses: wild type BALB/c mice exhibit a strong Th2 immune response and the IL-4 deficient C57BL/6 mice exhibit a Th1 response. We also excluded a role for antibodies in resistance through infection of B-cell deficient C57BL/6 mice. Our data suggest that the mechanisms that determine parasite clearance in a resistant/non-permissive host are Th2 dependent but that in a susceptible/permissive host, the parasite can develop in the face of a Th2 dominated response.
Institute of Cell, Animal and Population Biology, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, UK.
Laetitia
L
Le Goff
Tracey J
TJ
Lamb
Andrea L
AL
Graham
Yvonne
Y
Harcus
Judith E
JE
Allen
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005368:Filariasis / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D005370:Filarioidea / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D020022:Genetic Predisposition to Disease; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008842:Microfilariae / Q000254:growth & development / Q000276:immunology; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma