UZZELL, Thomas; STOLZENBERG, Ethan D.; SHINNAR, Ann E.*; ZASLOFF, Michael; Academy of Natural Sciences, Philadelphia; Univ. of Pennsylvania School of Medicine, Philadelphia; Barnard College, Columbia University, New York; Georgetown Univ. Medical Center, Washington, DC: Innate and Adaptive Immunity in Hagfish: Role of Cathelicidin Antimicrobial Peptides in the Hagfish Gut

Hagfish are primitive craniates that lack essential components of the vertebrate adaptive immune system such as thymus tissues and immunoglobulin genes. These living members of the Superclass Agnatha scavenge decaying marine animals and are likely to encounter potential pathogens in their diet. In our ongoing search for antimicrobial compounds involved in innate immunity, we previously isolated three potent broad-spectrum antimicrobial peptides (hagfish intestinal antimicrobial peptides, HFIAP-1, -2, and -3) from the intestinal tissues of Myxine glutinosa (Atlantic hagfish). Through cloning and cDNA analysis, we have now established that HFIAPs are early members of the cathelicidin family of antimicrobial peptides, hitherto known only in mammals. Their presence in hagfish, which are probably a sister group to the remaining Craniata, suggests an age for this gene family of ~500 Myr. In situ hybridization reveals that these hagfish cathelicidins are produced in nests of myeloid cells surrounding a portal system which drains the intestinal tract. The architecture of these cellular nests within the loose connective tissue of the gut wall is reminiscent of both gut-associated lymphoid tissue (GALT) and spleen of vertebrates. We suggest that this tissue organization provides local defense of Myxine‘s gastrointestinal tract via innate immunity and possibly served as the architectural plan upon which the adaptive immune system evolved.