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.

The iron chelator deferoxamine (DFO) B enhances virulence of Yersinia enterocolitica and modulates cellular immune responses. Since cytokines mediate effector mechanisms in resolution of yersiniae from infected tissues, the impact of DFO B and DFO G1 on cytokine production by murine bone marrow macrophages (BMM) was investigated. BMM were stimulated with lipopolysaccharide (LPS) of Salmonella typhimurium or infected with Y. enterocolitica. DFO B inhibited interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-alpha mRNA production 4-fold (shown by semiquantitative reverse transcription polymerase chain reaction). TNF-alpha and IL-6 protein production was reduced 50% by DFO B. In contrast, DFO G1 had no effect on cytokine production. Moreover, cytokine production by Yersinia-infected BMM was decreased by plasmid-encoded Yersinia proteins. Thus, plasmid-cured strains induced higher cytokine responses in BMM than did the wild type strain. These results suggest that DFO B acts in a bimodal fashion in yersiniosis: iron supply to the pathogen and immunosuppression of the host.

Campylobacter jejuni is one of the most common enterocolitis-causing microorganisms worldwide. It is of particular importance in immunodeficient patients, who frequently are prone to develop extraintestinal manifestations. Since these cases respond poorly to antibiotic treatment, a supportive immunomodulating therapy including the administration of C. jejuni-specific immunoglobulins would be desirable. In the present study, nine commercial immunoglobulin preparations for intravenous use were tested for the presence of C. jejuni lipopolysaccharide (LPS)-and outer membrane protein (OMP)-specific antibodies by using immunoblot and enzyme-linked immunosorbent assay techniques. The immunoglobulin G (IgG) antibody reactivities against these antigens were comparable in eight of nine tested immunoglobulin preparations. Only in one preparation were C. jejuni OMP-and LPS-specific IgM antibodies found. In this preparation the immunoblot test revealed a strong reactivity against both flagellin and a major OMP. Moreover, all immunoglobulin preparations recognized OMPs of C. jejuni serotypes Lior 4, 9, 11, and 29 equally strongly, while the reactivity to an anti-Lior 36 isolate was less marked. Furthermore, the bactericidal properties of three immunoglobulin preparations were tested by means of chemiluminescence signaling in and bacterial killing by human polymorphonuclear leukocytes (PMNL). The results show that the IgM preparation enhanced Campylobacter-triggered chemiluminescence signaling in PMNL as well as killing of C. jejuni by PMNL, while the other immunoglobulin preparations did not do so. These results suggest that the administration of immunoglobulin preparations containing C. jejuni-specific IgM antibodies would be beneficial for patients with severe C. jejuni infections.

An unusual hippurate-negative strain of Campylobacter jejuni caused a chronic refractory infection in a patient with X-linked agammaglobulinemia; this infection persisted for > 2 years despite therapy with various antibiotics and immunoglobulins (Igs). To characterize the defense status of this patient, several in vitro studies, including those with T cells and polymorphonuclear leukocytes (PMNLs), were performed. T cell responses specific for C. jejuni were only weak in this patient. Chemiluminescence and bacterial killing studies with PMNLs revealed that the bactericidal activity of PMNLs against Campylobacter was enhanced more vigorously by maternal serum than by commercial Ig preparations. On the basis of these results, combined treatment with ciprofloxacin and maternal plasma was initiated, and the C. jejuni infection was rapidly cured. This case report shows that in vitro immunologic assays may be useful for characterizing immune functions of patients with chronic or refractory C. jejuni infections, thus leading to individual treatment strategies.