Protective immunity against Helicobacter is characterized by a unique transcriptional signature.
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.
Mueller
Anne
A
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
O'Rourke
Jani
J
Chu
Pauline
P
Kim
Charles C
CC
Sutton
Philip
P
Lee
Adrian
A
Falkow
Stanley
S
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
D001428:Bacterial Vaccines; D002772:Cholera Toxin