Alterations in lymphocyte phenotype and function in children with shigellosis who develop complications.

This study was designed to see whether alterations occur in peripheral blood mononuclear cell phenotype and function in children with Shigella dysenteriae 1 infection with complications (leukemoid reaction and/or hemolytic-uremic syndrome) and whether there are any alterations prior to the development of complications. The following groups of children (ages, 12 to 60 months) were compared: children without any infection (n = 51), children with uncomplicated shigellosis (n = 65), children admitted with complicated shigellosis (leukemoid reaction and/or hemolytic-uremic syndrome) (n = 29), and children with shigellosis who developed complications after enrollment (subsequently complicated shigellosis) (n = 12). Tests for the peripheral blood mononuclear cell phenotype (CD3, CD4, CD8, CD57 [corrected], CD20, and CD25), spontaneous proliferation, and the proliferative response to phytohemagglutinin, pokeweed mitogen, and the lipopolysaccharide of S. dysenteriae 1 were performed, as were skin tests for delayed-type hypersensitivity (DTH). Children who subsequently developed complications differed from other groups of children as follows: (i) the numbers of CD3+ and CD4+ cells were lower than in uninfected children (P < 0.05), (ii) the CD4/CD8 ratio was lower than in children with uncomplicated shigellosis (P < 0.05) and in uninfected children (P < 0.05), and (iii) the levels of spontaneous proliferation of peripheral blood mononuclear cells were higher and DTH responses were lower than those in children with uncomplicated shigellosis (P < 0.05 and P < 0.017, respectively). Children with complications differed by having (i) increased numbers of CD3- CD57- [corrected] CD20- cells (P < 0.05) compared with those in other groups of children and (ii) lower CD4/CD8 ratios (P < 0.05), higher levels of spontaneous proliferation (P < 0.05), and lower DTH responses (P = 0.005) than children with uncomplicated shigellosis. Three to five days after enrollment, the number of CD4+ cells increased in children who subsequently developed complications (P = 0.025), i.e., when they developed complications and at this time their CD4+ cell number was similar to that of other groups of children. Thus, lymphocyte phenotype and function are altered prior to the development of complications in children with shigellosis, and once complications develop, the pattern of alterations changes. Whether these alterations have a role in precipitating complications or whether they reflect early events underlying the development of complications remains to be elucidated.

Peripheral blood neutrophil responses in children with shigellosis.

Alterations in peripheral blood neutrophil function are known to occur in patients with colitis and may have a role in precipitating nonspecific tissue injury. It is not known whether neutrophil function is altered in patients with Shigella dysenteriae type 1 infection, during which there is extensive colitis and which may be associated with life-threatening complications in young children. Three aspects of peripheral blood neutrophil function, polarization, attachment to yeast particles, and locomotion, were therefore studied in 111 children with S. dysenteriae type 1 infection and 57 children without any infection. All children were aged 12 to 60 months. Of the children with S. dysenteriae type 1 infection, 42 had leukemoid reaction, hemolytic-uremic syndrome, or septicemia (complicated shigellosis), while the others did not (uncomplicated shigellosis). Polarization and locomotion in the absence of chemoattractants and in response to N-formylmethionyl-leucylphenylalanine (FMLP) and the lipopolysaccharide (LPS) of S. dysenteriae type 1 were determined. Attachment to unopsonized and opsonized yeast particles was also determined. Children with shigellosis (uncomplicated or complicated) had more polarized neutrophils with and without chemoattractants than uninfected children (P < 0.05). Children with complicated shigellosis had more polarized neutrophils with FMLP at 10(-7) and 10(-6) M (P < 0.05) and with LPS than children with uncomplicated shigellosis (P < 0.05). At 3 to 5 days after enrollment, the numbers of polarized neutrophils with 10(-8), 10(-6), and 10(-5) M FMLP declined in children with uncomplicated shigellosis but not in those with complicated shigellosis. Attachment to yeast particles was similar in all three groups of children. Locomotion was inhibited by LPS in children with shigellosis (P < 0.05), whether it was uncomplicated or complicated, compared with locomotion in uninfected children. Finally, neutrophil polarization in uninfected children was negatively influenced by nutritional status. Thus, poorly nourished uninfected children had more polarized neutrophils with FMLP at 10(-9) M (P < = 0.02) and 10(-5) M (P = 0.043) than their better-nourished counterparts. In summary, altered neutrophil responses are associated with both uncomplicated and complicated shigellosis.