Role of IFN-gamma and IL-6 in a protective immune response to Yersinia enterocolitica in mice.
BACKGROUND
Yersinia outer protein (Yop) H is a secreted virulence factor of Yersinia enterocolitica (Ye), which inhibits phagocytosis of Ye and contributes to the virulence of Ye in mice. The aim of this study was to address whether and how YopH affects the innate immune response to Ye in mice.


RESULTS
For this purpose, mice were infected with wild type Ye (pYV+) or a YopH-deficient Ye mutant strain (DeltayopH). CD11b+ cells were isolated from the infected spleen and subjected to gene expression analysis using microarrays. Despite the attenuation of DeltayopH in vivo, by variation of infection doses we were able to achieve conditions that allow comparison of gene expression in pYV+ and DeltayopH infection, using either comparable infection courses or splenic bacterial burden. Gene expression analysis provided evidence that expression levels of several immune response genes, including IFN-gamma and IL-6, are high after pYV+ infection but low after sublethal DeltayopH infection. In line with these findings, infection of IFN-gammaR-/- and IL-6-/- mice with pYV+ or DeltayopH revealed that these cytokines are not necessarily required for control of DeltayopH, but are essential for defense against infection with the more virulent pYV+. Consistently, IFN-gamma pretreatment of bone marrow derived macrophages (BMDM) strongly enhanced their ability in killing intracellular Ye bacteria.


CONCLUSIONS
In conclusion, this data suggests that IFN-gamma-mediated effector mechanisms can partially compensate virulence exerted by YopH. These results shed new light on the protective role of IFN-gamma in Ye wild type infections.
Matteoli
Gianluca
G
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany. gianluca.matteoli@ifom-ieo-campus.it
Fahl
Edda
E
Warnke
Philipp
P
Müller
Steffen
S
Bonin
Michael
M
Autenrieth
Ingo B
IB
Bohn
Erwin
E
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D039481:CD11b Antigen / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D013154:Spleen / Q000166:cytology; D015009:Yersinia Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000235:genetics / Q000276:immunology*
D001425:Bacterial Outer Membrane Proteins; D039481:CD11b Antigen; D015850:Interleukin-6; D007371:Interferon-gamma; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia