title: Protective immunity against Helicobacter is characterized by a unique transcriptional signature.
abstract: Immunization with a whole-cell sonicate vaccine of Helicobacter felis in conjunction with cholera toxin as a mucosal adjuvant induces long-term protective immunity in a majority of laboratory mice. We have combined gene expression profiling and immunohistochemical analysis on a set of immunized animals to better understand the mechanism of protection. The stomachs of protected animals exhibited a strikingly different transcriptional profile compared with those of nonprotected or control mice, indicating that vaccination targets the appropriate site and leaves a molecular signature. Among the genes whose up-regulation is significantly correlated with protection are a number of adipocyte-specific factors. These include the fat-cell-specific cytokines adipsin, resistin, and adiponectin and the adipocyte surface marker CD36. Interestingly, potentially protective T and B lymphocytes can be found embedded in the adipose tissue surrounding protected stomachs but never in control or unprotected stomachs. Adipsin-specific immunohistochemical staining of protected stomach sections further revealed molecular cross-talk between adjacent lymphoid and adipose cell populations. We propose a mechanism of protection that involves the effector responses of either or both lymphocyte subclasses as well as the previously unappreciated paracrine functions of adipose tissue surrounding the resident lymphocytes.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Sherman Fairchild Science Building D-033, 299 Campus Drive, Stanford, CA 94305-5402, USA. muellera@stanford.edu
authors.forename: Anne
authors.initials: A
authors.lastname: Mueller
authors.forename: Jani
authors.initials: J
authors.lastname: O'Rourke
authors.forename: Pauline
authors.initials: P
authors.lastname: Chu
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kim
authors.forename: Philip
authors.initials: P
authors.lastname: Sutton
authors.forename: Adrian
authors.initials: A
authors.lastname: Lee
authors.forename: Stanley
authors.initials: S
authors.lastname: Falkow
mesh_terms: D017667:Adipocytes / Q000276:immunology; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage; D002772:Cholera Toxin / Q000008:administration & dosage; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D044922:Helicobacter felis / Q000276:immunology* / Q000472:pathogenicity; D018928:Immunity, Mucosal / Q000235:genetics*; D007114:Immunization; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014158:Transcription, Genetic
chemical_list: D001428:Bacterial Vaccines; D002772:Cholera Toxin