Cell type-specific effects of Yersinia pseudotuberculosis virulence effectors.
One important feature of Yersinia pseudotuberculosis that enables resistance against the host immune defence is delivery of the antiphagocytic effectors YopH and YopE into phagocytic cells. The tyrosine phosphatase YopH influences integrin signalling, and YopE impairs cytoskeletal dynamics by inactivating Rho GTPases. Here, we report the impact of these effectors on internalization by dendritic cells (DCs), which internalize antigens to orchestrate host immune responses. We found that this pathogen resists internalization by DCs via YopE. YopH that is important for blocking phagocytosis by macrophages and neutrophils and which is also present inside the DCs does not contribute to the resistance. However, the YopH targets Fyb and p130Cas show higher expression levels in macrophages than in DCs. Furthermore, live cell microscopy revealed that the cells internalize Y. pseudotuberculosis in different ways: the macrophages utilize a locally restricted receptor-mediated zipper mechanism, whereas DCs utilize macropinocytosis involving constitutive ruffling that randomly catches bacteria into membrane folds. We conclude that YopH impacts early phagocytic signalling from the integrin receptor to which the bacterium binds and that this tight receptor-mediated stimulation is absent in DC macropinocytosis. Inactivation of cytoskeletal dynamics by YopE affects ruffling activity and hence also internalization. The different modes of internalization can be coupled to the major functions of these respective cell types: elimination by phagocytosis and antigen sampling.
Fahlgren
Anna
A
Department of Molecular Biology and The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, S-90187 Umeå, Sweden.
Westermark
Linda
L
Akopyan
Karen
K
Fällman
Maria
M
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis; D017027:Protein Tyrosine Phosphatases / Q000276:immunology / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism*; D015011:Yersinia pseudotuberculosis / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology
D001425:Bacterial Outer Membrane Proteins; D037521:Virulence Factors; C063239:yopE protein, Yersinia; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia