ABSTRACT
There
has been a prevailing perception that Th1 and Th2 immune responses
induce antagonistic immune effector mechanisms during an infection. We
investigated the role of the Th1 cytokine gamma interferon
(IFN-γ) and the Th2 cytokine interleukin-5 (IL-5) in murine
filariasis infections with the rodent filarial nematode
Litomosoides sigmodontis with regard to immune responses to
the parasite. Earlier data showed an important role for IL-5 and
IFN-γ in effective immune responses to filarial infection.
Therefore, in this study it was asked whether IL-5 and IFN-γ
act synergistically or antagonistically. Indeed, IL-5 as well as
IFN-γ knockout (KO) mice show a higher worm load than the
wild-type controls. IFN-γ/IL-5 double-KO mice had a
significantly higher worm load than any of the single-KO mice,
suggesting a synergism between IFN-γ and IL-5 in controlling
worm infection. Neutrophils are known to play an important role for the
containment and encapsulation process of the worms. In infected
IFN-γ KO, IL-5 KO, and IFN-γ/IL-5 double-KO mice,
neutrophils were significantly reduced in chemotactic activity levels
compared to controls. In addition, the level of phagocytosis activity
of neutrophils from IFN-γ/IL-5 double-KO mice was further
decreased in comparison to that of the single-KO mice. Levels of tumor
necrosis factor alpha, which is an important factor for neutrophil
activation, were found to be reduced in macrophages from KO mice. In
conclusion, these results argue for immune effector mechanisms in
murine filarial infection that are dependent on both IFN-γ and
IL-5. Synergistic effects of the two cytokines may be mediated, at
least in part, by neutrophils for the control of adult
worms.
Synergism ofGamma Interferon and Interleukin-5 in the Control of MurineFilariasis
