# The Alterations in CD14 Expression in Periodontitis:
## 4 Discussion  
Disease manifestations through bacterial infections can take various forms including, but not limited to, direct effects of bacterial products, alterations of the host in response to the organism, and/or the persistent response of the hosts immune system after the clearance of the organism [55]. Though the mechanisms of the inflammatory host response have been extensively studied, CD14 remains a fascinating molecule whose functions and associations in role to periodontitis remain somewhat elusive. CD14 serves as an assessor molecule for different TLRs and facilitates the recognition of different bacterial components [56; 57]. Additionally, CD14 monocytes are important precursor cells from osteoclast development, which subsequently, in combination with osteoblasts, play an integral role in bone homeostasis. Hence further solidifying its role periodontal disease. Recently the role of sCD14 transducing and activating passage ways that could influence osteoclast genesis have been proposed [58]. In this systematic review, peripheral monocytes, serum, saliva, GCF, and tissue biopsies were chosen as subsets, as they are all thought to reflect different aspects of inflammatory response. Prior studies suggest that there is an increase in the percentage of monocytes in the peripheral blood of patients with chronic periodontitis [59]. Saliva has been actively scrutinized for its potential in primary diagnostics, exposing possible markers for early diagnosis of periodontal disease [60]. GCF is a filtrate of blood and an exudate of the inflamed periodontal tissue [61]. It has been used as a promising site-specific intermediate that exposes how the local host responses react to microbial challenges such as it can be found in periodontitis [62]. Thus, it was the goal of this systematic review to assess and examine local sCD14 and mCD14 levels in different tissues, physiological fluids, and periodontal compartments. Membrane-bound CD14 has been thought to only be expressed on circulating monocytes and tissue macrophages [9]. It is one of the factors, which facilitates the recognition of LPS by TLR-4 of host cells [10]. The expression of mCD14 in peripheral monocytes was analyzed, and results indicate that in four reports the expression of mCD14 on monocytes is decreased in periodontitis [19; 20; 22; 24], while two additional reports note no difference [18; 21]. In contrast to mCD14 expression in peripheral blood monocytes, the majority of studies on sCD14 levels in various biological fluids show a positive association between sCD14 levels and periodontal disease. This might be interpreted as an increase in production of sCD14 in cases with moderate-to-severe and generalized periodontal breakdown. The local levels of sCD14 measured in saliva and GCF are also affected by periodontitis. In two studies enhanced levels of sCD14 in periodontitis patients compared to healthy controlswere found [26; 27]. Furthermore, scaling and root-planning led to the decrease of salivary sCD14 levels, which underlies a positive association with periodontal disease [27]. The data on sCD14 levels in GCF are less conclusive [23; 25].These inconsistencies could be explained by differences in small sample size, variations in individual profiles, cite specific difference in GCF composition and generally complicated procedure of GCF collection [63]. Interestingly, one study also hypothesized and explored the concept of in vivo cleavage of CD14 during periodontitis [23]. Particularly, immunoreactive CD14 fragments were present in certain GCF samples of advanced (pocket depth \(\geq\)7 mm) periodontitis patients. Further, susceptibility to degradation by _Pgingivalis_ outer membrane vesicles was demonstrated, indicating that the CD14 receptor was highly sensitive to the proteinases associated with _P. gingivalis_. Thus, one could hypothesize that cleaving of mCD14 from monocytes might result in decreased phagocytosis and pathogen elimination, subsequently allowing easier reproduction of bacteria through a \"weakening\" of CD14 efficacy.