TY - JOUR
T1 - Immune serum-activated human macrophages coordinate with eosinophils to immobilize Ascaris suum larvae
AU - Coakley, Gillian
AU - Volpe, Beatrice
AU - Bouchery, Tiffany
AU - Shah, Kathleen
AU - Butler, Alana
AU - Geldhof, Peter
AU - Hatherill, Mark
AU - Horsnell, William G C
AU - Esser-von Bieren, Julia
AU - Harris, Nicola Laraine
N1 - © 2020 John Wiley & Sons Ltd.
PY - 2020/5/11
Y1 - 2020/5/11
N2 - Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.
AB - Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.
UR - http://www.scopus.com/inward/record.url?scp=85085516813&partnerID=8YFLogxK
U2 - 10.1111/pim.12728
DO - 10.1111/pim.12728
M3 - Article
C2 - 32394439
SN - 0141-9838
VL - 42
SP - e12728
JO - Parasite Immunology
JF - Parasite Immunology
IS - 7
M1 - e12728
ER -