**3.** *Chlamydia pneumoniae* **(CP) and atherosclerosis**

#### **3.1 Is CP just a respiratory tract infection agent?**

Chlamydia species are gram-negative obligate intracellular bacteria [20]. They can cause infections in both humans and animals. The Chlamydia pneumonia (CP) and the *Chlamydia trachomatis* (CT) are the most common species responsible for the human infections. Particularly, the CT has a serious socioeconomical burden due to its infections are sexually transmitted [21]. The CT is the most important cause of nongonococcic urethritis in males and also, it is an important cause of cervicitis in females [22]. The control of the CT infection is challenging because the half of the infected patients are asymptomatic [23].

CP commonly causes respiratory disease such as pneumonia, bronchitis, sinusitis, and pharyngitis. According to literature data, it is estimated about the CP is the cause of 10% of community acquired pneumonia. Most of the population were infected during childhood period, and the vast majority of the adult people have serologic evidences of past infection [24]. Biological evidences of CP in atheromatous plaques, and even in influenced areas of Alzheimer's disease patients brain, cogitate about that agent could not be a just respiratory tract infection agent [25, 26].

The infectious form of CP, the elementary body (EB) which is metabolically inactive, enters the body with inhalation and attaches to mucosal surface. After receptor mediated endocytosis enters into the cells and differentiates into metabolic active form, which is called the reticulate body (RB). The RB is the replicating form of CP and it is capable of modifying host cell pathways. The final EBs are released by cell lysis after 48 to 72 hours to infect other cells. The CP can infect respiratory epithelium, vascular endothelial cells, smooth muscle cells, monocytes, and macrophages. The CP can remain persistent in the host cell by escaping cellular lysosomal pathways. Resistance of CP to the host defense mechanisms determines the chronic infectious state [27, 28]. Intracellular survival of CP in cells of pulmonary alveolar membrane may be a reservoir for the persistent infectious state [29]. CP persistence is described as long-term survival of these metabolic inactive forms in the host cells. These patients are culture negative and the infection is antibiotic resistant due to reduced ribosomal activities [30].

CP can able to spread systemically *via* bacteremia during severe pulmonary infection and could be carried from recirculating monocytes/macrophages derived from alveolar membrane [31].
