title: Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection.
abstract: Passage of helminth larvae through the lungs can cause pulmonary eosinophilia that may have evolved as a means of parasite attrition. If allergic responses represent a misdirected activation of this arm of the immune system, then mechanisms governing eosinophil recruitment during infection would be expected to be closely related to those seen in allergy. We studied primary Necator americanus infection and compared this to multiply-infected or vaccinated mice. The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which was greatly enhanced in previously sensitized mice. Interestingly, the presence of larvae in the lung was sufficient to trigger eosinophil chemoattractant production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced by prior exposure to the parasites. Infection stimulated IL-5 production in all groups; however, this and IgE production were greatly enhanced in sensitized animals. Elevated IL-5 increased bone marrow production of eosinophils, and eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore, trapping of larvae in the pulmonary vasculature is sufficient to trigger eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2 immunity does not increase local chemokine production, but does increase IL-5 production, which greatly enhances the availability of eosinophils for recruitment to the lung.
authors: Leukocyte Biology Section, Biomedical Sciences Division, Imperial College Faculty of Medicine, London, GB. f.culley@ic.ac.uk
authors: Fiona J
authors: FJ
authors: Culley
authors: Alan
authors: A
authors: Brown
authors: Nadine
authors: N
authors: Girod
authors: David I
authors: DI
authors: Pritchard
authors: Timothy J
authors: TJ
authors: Williams
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000947:Antigens, Helminth / Q000008:administration & dosage; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000097:blood; D007814:Larva / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017221:Necator americanus / Q000276:immunology / Q000472:pathogenicity; D009332:Necatoriasis / Q000150:complications* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000209:etiology* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D007073:Immunoglobulin E