neonate intestinal immune response to cpg oligodeoxynucleotide stimulation新生儿肠道免疫反应cpg oligodeoxynucleotide刺激.pdfVIP

Neonate Intestinal Immune Response to CpG Oligodeoxynucleotide Stimulation ´ Sonia Lacroix-Lamande*, Nicolas Rochereau, Roselyne Mancassola, Mathieu Barrier, Amandine Clauzon, Fabrice Laurent ˆ ´ ´ ´ Laboratoire Controle et Immunologie des Maladies Enteriques du Nouveau-ne, UR1282 Infectiologie Animale et Sante Publique, INRA de Tours, Nouzilly, France Abstract Background: The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN) motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells. However, little is known about the efficacy of these molecules in stimulating the intestinal immune system in neonates. Methodology/Principal Findings: First, newborn mice received CpG-ODN orally, and the intestinal cytokine and chemokine response was measured. We observed that oral administration of CpG-ODN induces CXC and CC chemokine responses and a cellular infiltration in the intestine of neonates as detected by immunohistochemistry. We next compared the efficiency of the oral route to intraperitoneal administration in stimulating the intestinal immune responses of both adults and neonates. Neonates were more responsive to TLR9-stimulation than adults whatever the CpG-ODN administration route. Their intestinal epithelial cells (IECs) indirectly responded to TLR9 stimulation and contributed to the CXC chemokine response,