The interactions of Anaplasma phagocytophilum, endothelial cells, and human neutrophils.

Michael J. Herron, Marna E Ericson, Timothy J Kurtti, Ulrike G Munderloh

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Ixodes scapularis ticks transmit Anaplasma phagocytophilum (Ap), agent of human granulocytic anaplasmosis (HGA). Invasion of neutrophil granulocytes (PMN) by Ap is the hallmark of the disease, but these short-lived phagocytes are not likely the sole cell type required for productive infection. We analyzed infection of microvascular endothelial cells during pathogenesis of anaplasmosis in vivo and in vitro. Organs from Ap-infected mice were processed for confocal microscopy 41 days p.i. Fluorescent labeling of heart and liver sections using anti-factor VIII and anti-MSP2 antibodies allowed colocalization of Ap and vascular endothelium, indicating infection. Ap rapidly invaded and grew within HMEC-1 human microvascular endothelial cells and readily transferred to PMN. Over 50% of PMN became infected within two hours of coincubation with HMEC-1. PMN adhered to, polarized, and migrated upon infected endothelial monolayers. The Ap receptor on human PMN is PSGL-1, and infected endothelial cells upregulate ICAM-1 (CD54), but the mechanisms of transfer of Ap remain unknown. To elucidate the cellular determinants involved, we tested relevant antibodies and lectins. Anti-PSGL-1 reduced infection of PMN, but did not inhibit adherence of PMN to Ap infected HMEC-1 cells while anti-CD18 did. Sialidase pretreatment increased, and EDTA and fucoidan decreased binding of Ap to HMEC-1, whereas several other lectins had no effect. An endothelial reservoir of Ap offers opportunities for ongoing, direct cell-to-cell infection of PMN, avoidance of host immune effectors, and completion of the Ap life cycle by infection of circulating leukocytes available for transfer to blood-feeding ticks.

Original languageEnglish (US)
Pages (from-to)374-382
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1063
DOIs
StatePublished - Dec 2005

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