<i>Cronobacter sakazakii</i> infection implicates multifaceted neuro-immune regulatory pathways of <i>Caenorhabditis elegans</i>.

The neural pathways of <i>Caenorhabditis elegans</i> play a crucial role in regulating host immunity and inflammation during pathogenic infections. To understand the major neuro-immune signaling pathways, this study aimed to identify the key regulatory proteins in the host <i>C. elegans</i> during <i>C. sakazakii</i> infection. We used high-throughput label-free quantitative proteomics and identified 69 differentially expressed proteins. KEGG analysis revealed that <i>C. sakazakii</i> elicited host immune signaling cascades primarily including mTOR signaling, axon regeneration, metabolic pathways (<i>let-363</i> and <i>acox-1.4</i>), calcium signaling <i>(mlck-1)</i>, and longevity regulating pathways (<i>ddl-2</i>), respectively. The abrogation in functional loss of mTOR-associated players deciphered that <i>C. sakazakii</i> infection negatively regulated the lifespan of mutant worms (<i>akt-1</i>, <i>let-363</i> and <i>dlk-1</i>), including physiological aberrations, such as reduced pharyngeal pumping and egg production. Additionally, the candidate pathway proteins were validated by transcriptional profiling of their corresponding genes. Furthermore, immunoblotting showed the downregulation of mTORC2/SGK-1 during the later hours of pathogen exposure. Overall, our findings profoundly provide an understanding of the specificity of proteome imbalance in affecting neuro-immune regulations during <i>C. sakazakii</i> infection.