Yops of Yersinia enterocolitica inhibit receptor-dependent superoxide anion production by human granulocytes

The virulence plasmid-borne genes encoding Yersinia adhesin A (YadA) and se veral Yersinia secreted proteins (Yops) are involved in the inhibition of p hagocytosis and killing of Yersinia enterocolitica by human granulocytes, O ne of these Yops, YopH, dephosphorylates multiple tyrosine-phosphorylated p roteins in eukaryotic cells and is involved in the inhibition of phagocytos is of Y, enterocolitica by human granulocytes. We investigated whether anti body- and complement-opsonized plasmid-bearing (pYV(+)) Y,enterocolitica in hibits O-2(-) production by human granulocytes in response to various stimu li and whether YopH is involved. Granulocytes were preincubated with mutant strains unable to express YadA or to secrete Yops or YopH, O-2(-) producti on by granulocytes during stimulation was assessed by measuring the reducti on of ferricytochrome c, PYV+ Y, enterocolitica inhibited O-2(-) production by granulocytes incubated with opsonized Y, enterocolitica or N-formyl-Met -Leu-Phe (f-MLP). This inhibitory effect mediated by pYV did not affect rec eptor-independent O-2(-) production by granulocytes in response to phorbol myristate acetate, indicating that NADPH activity remained unaffected after activation of protein kinase C. The inhibition of f-MLP-induced O-2(-) pro duction by granulocytes depends on the secretion of Yops and not on the exp ression of YadA. Insertional inactivation of the yopH gene abrogated the in hibition of phagocytosis of antibody- and complement-opsonized Y. enterocol itica by human granulocytes but not of the f-MLP-induced O-2(-) production by granulocytes or tyrosine phosphorylation of granulocyte proteins. These findings suggest that the specific targets for YopH are not present in f-ML P receptor-linked signal transduction and that other Yop-mediated mechanism s are involved.