Molecular Immunology 44 (2007) 295–301 Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus aureus infection: Striking similarities and obvious differences with mammals Bin Lin 1 , Shangwu Chen 1 , Zhen Cao, Yiqun Lin, Dunzhou Mo, Haibo Zhang, Juda Gu, Meiling Dong, Zehuan Liu 2 , Anlong Xu ∗ State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Therapeutic Functional Genes, The Open Laboratory for Marine Functional Genomics of State High-Tech Development Program, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 W. Xingang Rd, Guangzhou 510275, PR China Received 17 February 2006; received in revised form 28 February 2006; accepted 9 March 2006 Available online 19 April 2006 Abstract Zebrafish has emerged as a valuable model for immunological studies. However, little is known about the overall picture of its immune response to infectious pathogens. Here we present the first systematic study of its immune response to Aeromonas salmonicida and Staphylococcus aureus,a Gram-negative and a Gram-positive bacteria, respectively. Genes induced upon infection were identified with suppression subtractive hybridization, with many of them encoding acute phase proteins (APPs). When compared with mammals, striking similarities and obvious differences have been observed. Both similar APPs (SAA, hepcidin and haptoglobin, etc.) and a similar system for the induction of APPs (which involves the TLRs, pro-inflammatory cytokines and C/EBPs) were identified, implying evolutionary conserved mechanisms among fish and mammals. Some novel APPs were also discovered, suggesting different immune strategies adopted by fish species. Among which, LECT2 was induced by up to 1000-fold upon infection, shedding new lights on the function of this gene. Our results constitute the first demonstration of a similar while different immune response in zebrafish and open new avenues for the investigation of evolutionary conserved and fish specific mechanisms of innate immunity. © 2006 Elsevier Ltd. All rights reserved. Keywords: Zebrafish; Acute phase response (APR); Innate immunity; Leukocyte cell-derived chemotaxin 2 (LECT2); Toll-like receptor 5 (TLR5) 1. Introduction Mouse, Drosophila melanogaster and C. elegans have been important models for immunological studies (Lemaitre et al., 1996; Kurz and Ewbank, 2003). Recently, zebrafish is also rec- ognized as a valuable model to understand immunity (Trede et al., 2004), and much progress has been made (Cosma et al., 2004; Danilova et al., 2005; Davis et al., 2002). However, lit- tle is known about the overall picture of its immune response Abbreviations: hpi, hour(s) post-infection; APR, acute phase response; APPs, acute phase proteins; CRP, C-reactive protein; SAP, serum amyloid P; SAA, serum amyloid A; LECT2, leukocyte cell-derived chemotaxin 2 ∗ Corresponding author. Tel.: +86 20 84113655; fax: +86 20 84038377. E-mail address: lssxal@mail.sysu.edu.cn (A. Xu). 1 These authors contributed equally to this work. 2 Present address: Research Center for Molecular Biology (RCMB), Jinan University, Guangzhou 510275, PR China. to infectious pathogens. Is it similar to or different from that of mammals? What, if any, are the similarities and differences? Additionally, is there any similarity with invertebrates such as Drosophila and C. elegans? The acute phase response (APR) is the immediate set of host inflammatory reactions that counteract challenges such as tis- sue injury, infection and trauma (Uhlar and Whitehead, 1999), including remarkable changes in the concentrations of many plasma proteins, known as the acute phase proteins (APPs) (Gabay and Kushner, 1999). APR has been extensively stud- ied in human and mouse. Some acute phase proteins were also isolated from some fish species (Bayne and Gerwick, 2001). However, no systematic study was performed and even less is known about zebrafish. Induction of APPs in mammals is mediated by Toll- like receptors (TLRs), pro-inflammatory cytokines and CCAAT/enhancer-binding proteins (C/EBPs). Upon infection, TLRs can recognize the microbial components thus sensing 0161-5890/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.molimm.2006.03.001