010 Citation: Varga MG, Lin HC (2020) The role of toll like receptor 9 in maintaining gut homeostasis. Ann Syst Biol 3(1): 010-014. DOI: https://dx.doi.org/10.17352/asb.000005 https://dx.doi.org/10.17352/asb DOI: LIFE SCIENCES GROUP Introduction The mucosal surfaces of the alimentary tract are perpetually challenged by antigens from environmental, dietary, microbial, and host-cell origins; any number of which have the capability of disrupting the relationship of the host with the delicate homeostatic environment of the gut. Yet, despite this perpetual bombardment, the immune response remains tightly controlled and poised to respond only to potential threats while remaining tolerant to the continuous presentation of foreign substances within the gut lumen. Intestinal Epithelial Cells (IECs) line the lumen of the small intestine and colon in a single layer, separating the gut luminal contents from the sterile environment of the lamina propria. While the epithelium primarily acts as a physical barrier, it also plays an integral response in mediating innate immune responses to the luminal microbiota. Toll-Like Receptors (TLRs) are critical components of the IEC innate immune response through their detection of highly specific pathogen associated molecular patterns (PAMPs) [1]. Toll-Like Receptor 9 (TLR9) is one such receptor whose cognate ligand is hypomethylated CpG DNA motifs (microbial cytosine-guanine dinucleotide (CpG)- DNA) [2], commonly found in bacterial and viral genomes. CpG/TLR9 refers then to the activation of TLR9 signaling by its cognate ligand. IECs are polarized, columnar cells with the apical surface facing the gut lumen and the basolateral surface facing the lamina propria. Both compartments of the IEC are highly specialized and serve distinct functions in maintaining gut homeostasis [3]. TLR9 is expressed in both compartments and serves dichotomous roles depending on the localization of its activation, whereby apical stimulation induces anti- inflammatory responses and basolateral stimulation induces pro-inflammatory responses [3]. The apical, anti- inflammatory responses can overcome pro-inflammatory signals transduced by other TLRs, highlighting the importance of TLR9 in maintaining gut homeostasis [3]. The microbiome in the large intestine is intimately associated with the IEC monolayer and thus regularly interacts with innate immune pattern recognition receptors without eliciting overt pro-inflammatory responses. This level of immune restraint, or tolerization, is due in large part to TLR9-mediated responses [4]. Thus, in this review, we seek to summarize the role of TLR9 in maintaining gut homeostasis in the face of the microbiome and how the utilization of this Abstract Toll-Like Receptor 9 (TLR9) is a unique pattern recognition receptor due to its ability to induce either pro- or anti-inflammatory cascades. However, much remains to be elucidated regarding this receptor, such as its localization in different cell and tissue types, the potential epitopes that induce signaling, and how activation of the receptor may result in diverging pathways. Despite these unknowns, the integral role of TLR9 in maintaining gut homeostasis remains clear. In addition to maintaining homeostasis, TLR9 may also have significant potential in treating gut-associated inflammatory diseases such as ulcerative colitis, Crohn’s and inflammatory bowel disease via its anti-inflammatory effects. This review will outline some of the key remaining questions regarding the role TLR9 in the gut and highlight its potential utility as a therapeutic target for gastrointestinal disease. Review Article The role of toll like receptor 9 in maintaining gut homeostasis Matthew G Varga 1 and Henry C Lin 2 * 1 Biomedical Research Institute of New Mexico, Albuquerque, NM 87108, USA 2 Medicine Service, New Mexico VA Health Care System and Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA Received: 26 February, 2020 Accepted: 26 March, 2020 Published: 28 March, 2020 *Corresponding author: Henry C Lin, MD, Medicine Service, New Mexico VA Health Care System and Divi- sion of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico, New Mexico VA Health Care System 1501 San Pedro Dr. SE Albuquerque, NM 87108 Albuquerque, NM 87131 USA, Tel: (505)-265-1711 ext. 4552; E-mail: Keywords: TLR9; Intestinal homeostasis; Bacterio- phage https://www.peertechz.com