International Immunology, Vol. 12, No. 6, 899-908,
June 2000
© 2000 Japanese Society for Immunology
A new mechanism for IL-5-dependent helminth control: neutrophil accumulation and neutrophil-mediated worm encapsulation in murine filariasis are abolished in the absence of IL-5
Bernhard-Nocht-Institute of Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
1 Division of Geographic Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
2 Department of Biochemical Pharmacology, University of Konstanz, 78434 Konstanz, Germany
Correspondence to: A. Hoerauf
IL-5 production and eosinophilia are features of helminth infections, but results concerning the role of IL-5 and eosinophils (EP) in worm control are contradictory. We describe here a novel, IL-5-dependent mechanism of helminth control in vivo, using a fully permissive murine filariasis model, i.e. infection of BALB/c mice with Litomosoides sigmodontis. Worm control was exerted by the formation of inflammatory nodules around adult filariae which initially remained alive but were eventually killed within several weeks. The cell population essential for inflammatory nodule formation was found to be neutrophils (NP) but not EP. Neutralization of IL-5 led to a failure of both EP and NP accumulation at the site of infection (i.e. the thoracic cavity), resulting in cessation of inflammatory nodule formation around worms and in their survival. The role of NP in this process was confirmed by treatment of mice with anti-granulocyte colony stimulating factor (G-CSF) which also resulted in a lack of inflammatory nodule formation and worm killing albeit in the presence of EP. Since IL-5, due to the absence of IL-5 receptors on NP, does not act on these cells directly, it was investigated if anti-IL-5 altered the production of NP-chemotactic cytokines. In anti-IL-5-treated mice, cytokines known to promote NP accumulation like tumor necrosis factor-
, G-CSF and KC (IL-8) were found to be strongly reduced, while NP-deactivating cytokines like IL-10 were increased. In conclusion, IL-5 constitutes a cytokine essential for NP-mediated worm control in filarial infection.
Keywords: animal model, cytokines, eosinophils, helminth infection, neutrophils
Transmitting editor: S. H. E. Kaufmann
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