title: Ivermectin-dependent attachment of neutrophils and peripheral blood mononuclear cells to Dirofilaria immitis microfilariae in vitro.
abstract: The macrocyclic lactones are the only anthelmintics used to prevent heartworm disease, but it is very difficult to reproduce their in vivo efficacy against Dirofilaria immitis larvae in experiments in vitro. These assays typically measure motility, suggesting that paralysis is not the mode of action of the macrocyclic lactones against D. immitis. We isolated peripheral blood mononuclear cells (PBMC) and neutrophils from uninfected dogs and measured their adherence to D. immitis microfilariae in the presence of varying concentrations of ivermectin. We found that adherence of PBMC to the microfilariae was increased in the presence of ivermectin concentrations ≥100 nM and adherence of neutrophils was increased in drug concentrations ≥10 nM. Up to 50% of microfilariae had adherent PBMC in the presence of the drug, and binding was maximal after 40 h incubation. Neutrophil adherence was maximal after 16 h, with approximately 20% of the microfilariae having at least one cell adhered to them. Adherent neutrophils showed morphological evidence of activation. These results are consistent with a model in which the macrocyclic lactones interfere with the parasites ability to evade the host's innate immune system.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA; Center for Tropical & Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Adriano F
authors.initials: AF
authors.lastname: Vatta
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Dzimianski
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Bob E
authors.initials: BE
authors.lastname: Storey
authors.affiliation: Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Melinda S
authors.initials: MS
authors.lastname: Camus
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Moorhead
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
authors.forename: Ray M
authors.initials: RM
authors.lastname: Kaplan
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA; Center for Tropical & Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA. Electronic address: adrianw@uga.edu.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Wolstenholme
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology; D004183:Dirofilaria immitis / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D006790:Host-Parasite Interactions / Q000187:drug effects*; D007107:Immune System / Q000187:drug effects / Q000469:parasitology; D007559:Ivermectin / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000469:parasitology*; D008842:Microfilariae / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000469:parasitology
chemical_list: D000977:Antiparasitic Agents; D007559:Ivermectin
keywords: Dirofilaria immitis; Macrocyclic lactones; Neutrophil; Peripheral blood mononuclear cell