Deficiency of innate immunity against P. aeruginosa enhances behavioral avoidance via the HECW-1/NPR-1 module in C. elegans

To antagonize infection of pathogenic bacteria in soil and confer increased survival, Caenorhabditis elegans employs innate immunity and behavioral avoidance synchronously as the two main defensive strategies. Although both biological processes and their individual signaling pathways have been partially elucidated, knowledge of their interrelationship remains limited. The current study reveals that deficiency of innate immunity triggered by mutation of the classic immune gene pmk-1 promotes avoidance behavior in C. elegans ; and vice versa. Restoration of pmk-1 expression using the tissue-specific promoters suggested that the functional loss of both intestinal and neuronal pmk-1 is necessary for the enhanced avoidance. Additionally, PMK-1 co-localized with the E3 ubiquitin ligase HECW-1 in OLL neurons and regulated the expressional level of the latter, which consequently affected the production of NPR-1, a G-protein-coupled receptor homologous to the mammalian neuropeptide Y receptor, in RMG neurons in a non-cell-autonomous manner. Collectively, our study illustrates, once the innate immunity is impaired when C. elegans antagonizes bacterial infection, the other defensive strategy of behavioral avoidance can be enhanced accordingly via the HECW-1/NPR-1 module, suggesting that GPCRs in neural circuits may receive the inputs from immune system and integrate those two systems for better adapting to the real-time status.

Neuropeptide Y receptor Y1 and Neuropeptide Y receptor Y5 are differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified both neuropeptide Y receptor Y1 and neuropeptide Y receptor Y5, encoded by NPY1R and NPY5R as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of NPY1R and NPY5R messenger RNA than did patients not treated with trastuzumab; a single administration of trastuzumab was sufficient to result in differential expression of NPY1R in primary tumors of the breast, demonstrating increased expression of neuropeptide receptors, the expression of one of which in the peripheral blood is correlated with metastasis in patients with breast cancer (5), as a transcriptional consequence of treatment with trastuzumab.