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The Enigmatic Eosinophil: Investigation of the Biological Role of Eosinophils in Parasitic Helmint Infection

The Enigmatic Eosinophil: Investigation of the Biological Role of Eosinophils in Parasitic Helmint Infection

Key words: eosinophilinterleukin-5interleukin-5 deficient mice – helminth – asthma

In many helminth infected hosts the number of eosinophils increases dramatically, often without any concurrent increases in the number of other leukocytes, so that eosinophils become the dominant cell type. Many experimental investigations have shown that the eosinophilia is induced by interleukin-5 (IL-5) but its functional significance remains unclear. Mice genetically deficient in IL-5 (IL-5-/-) have been used to evaluate the functional consequences of the IL-5 dependent eosinophilia in helminth infected hosts. Host pathology and level of infection were determined in IL-5-/- and wild type mice infected with a range of species representative of each major group of helminths. The effects of IL-5 deficiency were very heterogeneous. Of the six species of helminth examined, IL-5 dependent immune responses had no detectable effect in infections with three species, namely the cestodes Mesocestoides corti and Hymenolepis diminuta and the trematode Fasciola hepatica. In contrast, IL-5 dependent immune responses were functionally important in mice infected with three species, notably all nematodes. Damage to the lungs caused by migrating larvae of Toxocara canis was reduced in IL-5-/- mice.

Infections of the intestine by adult stages of either Strongyloides ratti or Heligmosomoides polygyrus were more severe in IL-5-/- mice. Adult intestinal nematodes were clearly deleteriously affected by IL-5 dependent processes since in its presence there were fewer worms which had reduced fecundity and longevity. The implications of these results for the viability of using inhibitors of IL-5 as a therapy for asthma are considered.

Eosinophils are non-dividing cells that arise in the bone marrow and then are released into the bloodstream where they typically make up only 2-5% of circulating leukocytes (Wardlaw & Moqbel 1992). In a fairly narrow range of conditions, notably in allergic states and following infection with multicellular parasites (helminths), the number of eosinophils increases dramatically. Eosinophil proliferation occurs without any concurrent increases in the number of other leukocytes so that eosinophils can become the dominant leukocyte (Dent et al. 1990, Sanderson 1991). The cytokine interleukin-5 (IL-5) is the major factor necessary for proliferation and activation of eosinophils in vivo (Sanderson 1992).

The cytoplasmic granules that are stained by eosin are the main distinguishing feature of eosinophils. These granules contain numerous cytotoxic proteins as well as pro- and anti-inflammatory mediators. Much of the pathology of asthma appears to be a consequence of inappropriate proliferation, activation and degranulation of eosinophils in the lungs (Desreumaux & Capron 1996, Foster et al. 1996, Martin et al. 1996). There is considerable hope that the pathology of asthma can be limited by treatments that inhibit IL-5. However, a number of observations suggest that IL-5, and the eosinophils it induces, are of fundamental biological importance. First, the sequence of IL-5 has been highly conserved among mammals (Sanderson 1994) and eosinophils or eosinophil-like cells are present in most vertebrates (Jones 1993). Second, IL-5 is an unusual cytokine as in vivo it appears to have an extremely narrow range of actions and other cytokines cannot fully compensate for its absence (Dent et al. 1990). Third, it is energetically demanding to mount an eosinophilia. As an eosinophilia characterises infection by helminths, it has long been thought that eosinophils kill helminths and that this is their raison d’être.