YERSINIA-PSEUDOTUBERCULOSIS INHIBITS FC RECEPTOR-MEDIATED PHAGOCYTOSIS IN J774 CELLS

Nonopsonized as well as immunoglobulin G (IgG)-opsonized Yersinia pseu dotuberculosis resists phagocytic uptake by the macrophage-like cell l ine J774 by a mechanism involving the plasmid-encoded proteins Yops. T he tyrosine phosphatase YopH was of great importance for the antiphago cytic effect of the bacteria. YopH-negative mutants did not induce ant iphagocytosis; instead, they were readily ingested, almost to the same extent as that of the translocation mutants YopB and YopD and the pla smid-cured strain. The bacterial determinant invasin was demonstrated to mediate phagocytosis of nonopsonized bacteria by these cells. In ad dition to inhibiting uptake of itself, Y. pseudotuberculosis also inte rfered with the phagocytic uptake of other types of prey: J774 cells t hat had been exposed to virulent Y. pseudotuberculosis exhibited a red uced capacity to ingest IgG-opsonized yeast particles. This effect was impaired when the bacterium-phagocyte interaction occurred in the pre sence of gentamicin, indicating a requirement for in situ bacterial pr otein synthesis. The Yersinia-mediated antiphagocytic effect on J774 c ells was reversible: after 18 h in the presence of gentamicin, the pha gocytic capacity of Yersinia-exposed J774 cells was completely restore d. Inhibition of the uptake of IgG-opsonized yeast particles was depen dent on the Yops in a manner similar to that seen for blockage of Yers inia phagocytosis. This similarity suggests that the pathogen affected a general phagocytic mechanism. Despite a marked reduction in the cap acity to ingest IgG-opsonized yeast particles, no effect was observed on the binding of the prey. Taken together, these results demonstrate that Yop-mediated antiphagocytosis by Y. pseudotuberculosis affects re gulatory functions downstream of the phagocytic receptor and thereby e xtends to other types of phagocytosis.