Biological roles of host defense peptides: lessons from transgenic animals and bioengineered tissues.

Host defense peptides (HDPs) have long been recognized as microbicidal agents, but their roles as modulators of innate and adaptive immunity have only more recently been appreciated. The study of transgenic animal and tissue models has provided platforms to improve our understanding of the immune modulatory functions of HDPs. Here, the characterization of transgenic animals or tissue models that over-express and/or are deficient for specific HDPs is reviewed. We also attempt to reconcile this data with evidence from human studies monitoring HDP expression at constitutive levels and/or in conjunction with inflammation, infection models, or disease states. We have excluded activities ascribed to HDPs derived exclusively from in vitro experiments. An appreciation of the way that HDPs promote innate immunity or influence the adaptive immune response is necessary in order to exploit their therapeutic or adjuvant potential and to open new perspectives in understanding the basis of immunity. The potential applications for HDPs are discussed.

Expression of TECK/CCL25 and MEC/CCL28 chemokines and their respective receptors CCR9 and CCR10 in porcine mucosal tissues.

CCL25 and CCL28 (also named TECK and MEC) are CC chemokines primarily expressed by thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, named CCR9 and CCR10, are mainly expressed on T lymphocytes for CCR9 and IgA(+) and IgM(+) plasmablasts for CCR9 and CCR10, respectively. In human and mouse, chemokines CCL25 and CCL28 play an important role in attracting immune cells to the gastrointestinal tract and in controlling segmental specialization of the intestinal immune system. To investigate if CCL25 and CCL28 play a similar role in the pig and to better understand lymphocyte trafficking in this species, we cloned porcine CCL25 and CCR10 and measured expression of CCL25, CCL28, CCR9, and CCR10 transcripts by real-time and conventional PCR in various tissues from newborn and young piglets, and adult sows. The results of the expression analyses show that (i) expression of CCL25 mRNA is mainly restricted to the small intestine, (ii) CCL28 mRNA expression is detectable in all tested epithelial mucosal surfaces with the highest levels of expression in the mammary gland, trachea and large intestine, (iii) high levels of expression of CCR9 mRNA in CD3+ T lymphocytes, gut-associated lymphoid tissues (GALT), and the small intestine, (iv) high levels of expression of CCR10 mRNA in GALT, the large intestine, the small intestine, and the mammary gland, and (v) up-regulation of CCL28 mRNA expression during lactation in the mammary gland. This pattern of expression, which is discussed in the context of compartmentalization of the porcine common mucosal immune system into upper aero-digestive tract, small intestine and large intestine, suggests a key role for CCL28 in the recruitment of IgA secreting cells into the mammary gland enabling the passive transfer of IgA antibodies from mother to infant.

Expression of mucosal chemokines TECK/CCL25 and MEC/CCL28 during fetal development of the ovine mucosal immune system.

CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system.