and are members of the family of obligate intracellular bacteria. or reticulate body (RB), respectively representing the extracellular and intracellular forms within its life cycle , as depicted in Figure 1. At EB phase, is small (0.2C0.6 m) and compact due to densely crosslinking cysteine-rich outer membrane proteins by disulphide bonds that form a supramolecular disulphide complex . The chlamydial EB is an osmotically BVT-14225 stable and metabolically dormant bacterium, this permits survival at harsh extracellular environments and facilitates its attachment and entry into the host cell. After entering a cell, the EB transforms into RB that is characterized by reduced supramolecular disulphide complex, and appears relatively larger (0.6C1.5 m) in size. In RB form, is osmotically fragile but metabolically active; this equips the bacteria for robust cell division through binary fission within inclusions [2,3]. The newly synthesized RBs will be converted to EBs in a process signaled by size reduction, where the RBs gradually decrease in size following multiple rounds of binary fission before differentiating into EBs . Toward the final stage of the developmental cycle, the EBs are released from the host cell through extrusion or cellular lysis to commence the developmental cycle anew . Open in a separate window Figure 1 Schematic diagram of the developmental cycle of to enter a persistent phase in which the RBs become aberrantly enlarged . Transcriptional profiling analyses showed that these atypically large RBs are metabolically active [7,8]. This has led to the suggestion that this may be a mode of growth whereby can be protected from the host defense mechanism while stockpiling nutrients in preparation for growth when the conditions become conducive to its replication . Additionally, can repurpose the host cell for its growth advantage. For instance, in human epithelial cells, it alters protein stability and proteome profile, including mammalian target of rapamycin (mTOR)-mediated pathway for energy production that facilitates RB replication in inclusion [10,11]. Strategies of immune evasion underlying chronic persistency of potentiate the pathogens long-term survival thus providing opportunity for bacterial dissemination from primary infectious site to a remote location . As a consequence, BVT-14225 infection-mediated pathologies extend beyond urogenital, eye, and pulmonary sites, and are associated with a gaining list of chronic inflammatory diseases, including reactive arthritis, atherosclerosis, multiple Goat Polyclonal to Rabbit IgG sclerosis, Alzheimers disease, asthma, and primary biliary cirrhosis, as summarized in Table 1. The current review focuses on the mechanisms of bacteria migration and pathogenesis of these diseases that occur at the secondary sites following and infections in human host. Table 1 The list of chronic inflammatory diseases associated with infection by the family. Presence of DNA, antigens, EB in the synovial fluid; elevated serum anti-antibodies in ReA patients [13,14,15]. i. hijacks monocytic cells as their trojan horses [16,17] to travel to synovium where hypoxic stress inhibits indoleamine BVT-14225 2,3-dioxygenase (IDO) activity [18,19] and nutrient starvation promotes bacteria persistency . i. Molecular mimicry between host and chlamydial HSP60 proteins [21,22] and presence of other antigens triggers robust secretion of inflammatory cytokines. AtherosclerosisPresence of in atherosclerotic plaques exacerbates disease pathology; elevated anti-antibodies among patients [23,24,25]. i. facilitates plaque formation by enhancing a firm adhesion of the monocyte to the endothelium  and promotes foam cells formation . i. accelerates development of atherosclerosis by activating TLR4 signaling pathway , and CD8+ T cells . i. adheres to platelets and causes aggregation that increases risk of atherosclerosis [28,29]. Multiple Sclerosis (MS)High percentage of positive infection using culture method;antibodies in MS patients [31,32,33,34]. Failure to detect bacteria in MS patients using.