Survival of Group BStreptococcusType III in Mononuclear Phagocytes: Differential Regulation of Bacterial Killing in Cord Macrophages by Human Recombinant Gamma Interferon and Granulocyte-Macrophage Colony-Stimulating Factor

Abstract

Phagocytic and killing capacities of resident and cytokine-activated human macrophages against group B Streptococcus (GBS) type III were studied. Evidence is presented that monocyte-derived macrophages from cord and adults ingest serum-opsonized GBS but that killing of bacteria was negligible in resident cells. Treatment of adult macrophages with recombinant human gamma interferon (rhIFN-␥; 100 U/ml) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml) resulted in significant increases of killing of GBS (P < 0.01 for each). The killing capacity of cord macrophages treated with rhGM-CSF was also enhanced compared to that of untreated cells (P < 0.01). However, treatment with rhIFN-␥ resulted in only a moderate increase in the capacity of cord macrophages to kill GBS (P > 0.1). These results mirrored the effect of rhIFN-␥ on candidacidal capacities of cord and adult macrophages, reported earlier from our laboratory. These data indicate differential modulation of neonatal macrophages by rhGM-CSF and rhIFN-␥. We suggest that administration of rhGM-CSF to neonates with invasive GBS disease may enhance host resistance to these bacteria.Group B streptococci (GBS) are the most common cause of deep-seated bacterial infection and sepsis in neonates (4,20). Over the last decade, the burden of invasive GBS disease in immunocompromised children and adults has also been increasing (24). In adults, common predisposing conditions for severe GBS infection and sepsis include malignant neoplasms, diabetes mellitus, human immunodeficiency virus type 1 infection, trauma, and older age (6,8,18). The mortality of invasive GBS disease in both newborns and adults remains high despite advances in intensive care and the susceptibility of the pathogen to penicillin (4,18,20).The propensity of GBS to cause invasive neonatal infections might be related to inappropriate opsonization due to the lack of maternally derived, type-specific antibodies (20). Polymorphonuclear neutrophil granulocytes play a key role in phagocytosis and eventual killing of streptococci and other extracellular pathogens. We reported earlier that a clinical isolate of GBS type III was rapidly ingested and killed by cord and adult granulocytes in the presence of serum opsonins (13). In contrast to what is found for granulocytes, the capacity of cord monocytes to kill GBS was decreased compared to that of adult blood monocytes (13). To gain more insight into the newborn's ability to resist infection by GBS, we studied various interactions between these bacteria and monocyte-derived macrophages isolated from the cord. Experiments were performed to study the effect of recombinant human gamma interferon (rhIFN-␥) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on phagocytosis and the bactericidal capacities of cord and adult macrophages. We show here that cord macrophages efficiently phagocytose serum-opsonized GBS but that the ingested bacteria survive inside the cells. Bacterial killing was augmented b...

Neonatal Innate Immunity to Infectious Agents

“…Earlier studies showed that the capacity of cord blood monocytes to kill serum-opsonized GBS type III was decreased compared to the capacity of adult blood monocytes (56). Interactions between serum-opsonized GBS and monocyte-derived macrophages isolated from cord blood were also studied by using resident and cytokine-activated cells (53). These results showed that resident cord and adult macrophages efficiently phagocytosed serum-opsonized GBS, but the ingested bacteria survived inside the cells.…”

Defective antigen-presenting cell function in human neonates

“…Importantly, this latter finding is associated with deficient killing of intra-cellular pathogens by IFN-γ-stimulated neonatal macrophages [24], which could have broad implications in vivo.…”

Phagocytosis and intracellular killing of heterogeneous vancomycin-intermediate Staphylococcus aureus strains

“…Phagocytosis of bacteria by granulocytes was measured as the percentage decrease in the number of viable extracellular bacteria in the phagocytic cell suspension (Maró di et al, 1983(Maró di et al, , 2000. Briefly, 200 ml granulocyte suspension (10 7 cells ml 21 ) was incubated with 200 ml bacterial suspension (10 7 bacteria ml 21 ) in the presence of various concentrations of serum at 37 uC under slow rotation (4 r.p.m.).…”