The impact of desferrioxamine B (DFOB) on intracellular calcium mobilization, chemoluminescence (CL) signaling, phagocytosis, and bacterial killing of Yersinia enterocolitica by polymorphonuclear leukocytes (PMNL) was investigated. DFOB did not alter calcium signaling in PMNL but transiently increased phagocytosis. Likewise, higher counts of viable bacteria in PMNL and increased CL signals after stimulation with Y. enterocolitica were observed in the presence of DFOB. However, DFOB reduced the CL signal elicited individually by zymosan, PMA, and FMLP. Comparison of plasmid-cured with plasmid-harboring Y. enterocolitica revealed that plasmid-encoded determinants modulate phagocytosis, CL signal, and bactericidal properties of PMNL. These data demonstrate that DFOB alters microbicidal properties of PMNL and modulates their interaction with Y. enterocolitica and provide further evidence for a putative dual role of DFOB in the pathogenesis of Yersinia infection, namely growth support of the pathogen and modulation of the antimicrobial host response.