ROLE OF YOPH IN THE SUPPRESSION OF TYROSINE PHOSPHORYLATION AND RESPIRATORY BURST ACTIVITY IN MURINE MACROPHAGES INFECTED WITH YERSINIA-ENTEROCOLITICA

Tyrosine phosphorylation is an important component of the signaling pa thways responsible for the activation of the macrophage respiratory bu rst, Because the virulence plasmid of Yersinia enterocolitica encodes a phosphotyrosine phosphatase, YopH, it is possible that the pathogeni c strategy of Y. enterocolitica involves the disruption of tyrosine ph osphorylation in the macrophage leading to inhibition of respiratory b urst activity. We have investigated the effects of Yersinia infection on tyrosine phosphorylation and respiratory burst activity in murine b one marrow-derived macrophages, Infection of macrophages with virulent [Ye(pYV(+))] but not avirulent [Ye(pYV(-))] strains of Y. enterocolit ica was found to suppress both tyrosine phosphorylation and respirator y burst activity in response to zymosan, Mutational inactivation of Yo pH reversed the suppressive effect of Ye(pYV(+)) on zymosan-induced ty rosine phosphorylation, indicating that YopH is responsible for the de phosphorylation of macrophage phosphotyrosine-containing proteins obse rved in macrophages infected with the virulent strain of Y. enterocoli tica. In contrast, mutational loss of YopH failed to reverse the inhib itory effect of Ye(pYV(+)) on the zymosan-triggered respiratory burst, We conclude that the inhibition of the macrophage respiratory burst b y Y. enterocolitica involves a plasmid-encoded virulence protein(s) ot her than, or in addition to, YopH.