Identification of novel signature genes attesting arsenic-induced immune alterations in adult zebrafish (Danio rerio)

Arsenic poisoning is a serious global issue. Apart from causing developmental and systemic toxicity, arsenic has recently been reported for its ability to hinder immune responses. The present study is designed to identify the global expression profile associated with arsenic-induced immune alterations at the organismic level. Adult zebrafish (Danio rerio) were exposed to 20, 40 and 80ppb of arsenic trioxide for 30days, sacrificed and global gene expression profile studied. Microarray data suggested 65 immune related genes were commonly affected in the three treatment regimens. The expression profile of key immune related genes (tlr1, nitr1f, nitr1c, crfb8, socs7, socs3b, abcb3/1, mch1uja, ifnγ1-2, cxcl12b and crlf1a) was validated by qPCR. Pathway analysis suggested the major involvement of JAK-STAT circuit in the process. The expression of these marker genes was also studied in arsenic exposed and bacteria (Aeromonas hydrophila) challenged zebrafish. Increase in bacterial colony forming units (CFU) coupled with gross histopathology of kidney in arsenic exposed-bacteria challenged fish suggested profound immuno-compromised condition. We propose that chronic arsenic exposure leads to hyperactivation of the immune system as a consequence when exposed to further stress (microbial) it induces immuno-suppression with pathological implications. The study provides a molecular snap shot for predicting arsenic immuno-toxicity.