Role of YopH in the suppression of tyrosine phosphorylation and respiratory burst activity in murine macrophages infected with Yersinia enterocolitica

Abstract

Tyrosine phosphorylation is an important component of the signaling pathways responsible for the activation of the macrophage respiratory burst. Because the virulence plasmid of Yersinia enterocolitica encodes a phosphotyrosine phosphatase, YopH, it is possible that the pathogenic strategy of Y. enterocolitica involves the disruption of tyrosine phosphorylation in the macrophage leading to inhibition of respiratory burst activity. We have investigated the effects of Yersinia infection on tyrosine phosphorylation and respiratory burst activity in murine bone marrow-derived macrophages. Infection of macrophages with virulent [Ye(pYV+)] but not avirulent [Ye(pYV-)] strains of Y. enterocolitica was found to suppress both tyrosine phosphorylation and respiratory burst activity in response to zymosan. Mutational inactivation of YopH reversed the suppressive effect of Ye(pYV+) on zymosan-induced tyrosine phosphorylation, indicating that YopH is responsible for the dephosphorylation of macrophage phosphotyrosine-containing proteins observed in macrophages infected with the virulent strain of Y. enterocolitica. In contrast, mutational loss of YopH failed to reverse the inhibitory effect of Ye(pYV+) on the zymosan-triggered respiratory burst. We conclude that the inhibition of the macrophage respiratory burst by Y. enterocolitica involves a plasmid-encoded virulence protein(s) other than, or in addition to, YopH.

Role of immune response in Yersinia pestis infection

“…TNF- is one of the most important proinflammatory cytokines, which plays a crucial role in limiting the severity of bacterial infection. In addition to YopP, YopM (an important virulence factor in Yersinia infection in mice) (40,41) interacts with protein kinase C-like 2 and ribosomal protein S6 kinase, which are also involved in proinflammatory signaling [42]. The suppression of proinflammatory factor production not only reduces the activation of NK cells and phagocytes, but also destroys the inflammatory environment that is very essential for the adaptive immune response [42].…”

Interaction between Yersinia pestis and the Host Immune System

“…At least four Yops (YopH, YopE, YopT, and YopO) are involved in inhibiting the phagocytosis of yersiniae, either by interfering with the host cell actin regulation of Rho GTPases (YopE, YopT, and YopO) or specifically and rapidly inactivating host proteins associated with signaling from the receptor to actin (YopH) (1,2,6,39,77). Moreover, YopH can suppress the production of reactive oxygen intermediates by macrophages and PMNs (35).…”

Inhibition of Yersinia Tyrosine Phosphatase by Furanyl Salicylate Compounds

“…The type III secretion system is a highly conserved macromolecular machinery found in many pathogenic Gram-negative bacteria and is induced by contact with a eukaryotic cell to inject effector Yops into the cytoplasm of the target cells (21). In the host cell, the Yops disrupt signaling cascades responsible for initiating key immune functions, such as phagocytosis (22)(23)(24), respiratory burst (25,26), cytokine production, and lymphocyte activation (27). As a consequence, both the innate and adaptive immune responses are seriously impaired (28).…”