Lampreys, one of the most basal jawless vertebrates, are an excellent animal model for investigating vertebrate evolution, embryonic development, and the origin of adaptive immunity. Gut-derived Shewanella strain was isolated and then proved to induce adaptive immunity response in lampreys. Using Shewanella as the antigen, the effect of gut-derived Shewanella on lamprey leukocyte proteome was investigated via label-free liquid chromatography–tandem mass spectrometry for quantitative proteomics analysis. Twenty-five differentially expressed proteins in lamprey leukocytes were identified with significant differences. The differentially expressed proteins were associated with several biological processes. Among these proteins, the signal transducer and activator of transcription 3 (STAT3) was significantly upregulated in leukocytes after Shewanella immunization, indicating that lamprey STAT3 (L-STAT3) was involved in Shewanella–lamprey interactions. Expression pattern analysis revealed that L-STAT3 was mainly distributed in the cytoplasm and upregulated in other tissues after Shewanella immunization. Moreover, L-STAT3 overexpression could promote HEK-293 T and HeLa cell proliferation. However, the functions of L-STAT3 in the adaptive immune response of lamprey induced by gut-derived Shewanella remain to be explored. Overall, the identification of leukocyte proteins involved in Shewanella–lamprey interactions provides important information for understanding the variable lymphocyte receptor-based adaptive immune signal pathways in lampreys. Significance Lampreys are considered to be an excellent animal model for studying the origin and development of adaptive immune systems in vertebrates. Lampreys use variable lymphocyte receptors (VLRs) in recognizing antigens. However, the understanding of the VLR-based adaptive immune signal pathways in lampreys remains unclear. Intestinal bacteria could regulate the development of host immune systems. The attempts of inducing lamprey leukocyte differentially expressed proteins using the gut bacterial as the antigen will supply an promising avenue to explore the molecular mechanism of the intestinal bacteria interaction with it's host. Also, the identification of differentially expressed proteins involved in interactions between gut-derived Shewanella and lamprey will supply clues for understanding the variable lymphocyte receptor-based adaptive immune signal pathways in lampreys.
