Brucellosis is caused by the Brucella. The bacterium is a gram-negative coccus that can parasitize in cells, infect livestock, cause abortion and infertility, and infect humans and cause convoluted fever, endocarditis, arthritis, and osteomyelitis. In recent years, many important discoveries have explained the interaction between Brucella and host cells to a certain extent, and people also have a certain understanding and understanding of the intracellular survival mechanism of Brucella.
Invasion of Brucella Abortus On Host Cells
The key to the pathogenic effect of Brucella abortus is that it can invade ordinary cells and phagocytic cells. Pathogens invade the body from the skin or mucous membranes and preferentially colonize macrophages in the intestinal mucosa. After phagocytosis by mucosal epithelial phagocytes, bacteria are transferred and transported to the lamina propria and submucosa.
Invasive Effect of Brucella Abortus On Phagocytes
In the opsonized state, macrophages take up Brucella primarily through Fc receptors or complement. Similar to other bacteria, its opsonization appears to be inversely proportional to Brucella survival and replication rates within macrophages. That is, Fc receptor- or complement-mediated phagocytosis appears to favor host cells rather than bacteria. In the unopsonized state, macrophages appear to take up Brucella via lectin receptors and fibronectin receptors. Opsonized Brucella can activate macrophages to lyse the pathogen by phagolysosome before it reaches the intracellular replication site. In contrast, unopsonized bacteria were more likely to survive and replicate within macrophages. Attenuated strains of abortive Brucella are able to adhere to and invade host cells, but they cannot survive inside phagocytes. Although Brucella abortus can invade epithelial cells and placental trophoblast cells, it is weaker than intracellular parasitic pathogens such as Salmonella enteritidis.
Invasion of Non-Phagocytic Cells by Brucella Abortus
Although the corresponding cellular receptors and bacterial ligands have not been found in non-phagocytic cells, there is evidence that some specific molecules are involved in the binding of Brucella to cells. The outer membrane protein with a molecular weight of 41 KDa is involved in the adhesion and invasion of Brucella to host cells. Studies have shown that the invasion of epithelial cells by Brucella requires the participation of an appropriate amount of actin. The invasion of non-phagocytic cells by Brucella requires the activation of Rho small GTPases (eg Rho, Rac, Cdc42). This group of GTPases, mainly some cytoskeletal regulators, is involved in the internalization process of a variety of intracellular parasites. Clearly, the condition for activation of Cdc42 is the direct contact between the host cell and the bacteria. The activation conditions for Rho and Rac, however, are indirect contact between host cells and bacteria. In addition, cyclic-GMP, PIP3 kinase, tyrosine kinase and MAP kinase are all second messenger transduction regulators, and they all reduce the internalization of Brucella in epithelial cells.
The Intracellular Survival Mechanism of Brucella Abortus
The long-term residence of pathogens in host phagocytes may be due to their adaptation to this harsh pH environment, nutrient deprivation, aerobic and nitrogen-mediated reactions, and lysosome lysis in the phagosome through their own genetic changes. The internalization process of Brucella abortus can change the transport pathway of Brucella in host cells, change the normal maturation process of phagosomes in host cells and interfere with the adhesion of phagolysosomes to Brucella. Studies have shown that Brucella cannot survive and replicate within neutrophils. This also shows that Brucella cannot be transported, survived and replicated in all phagocytes. However, Brucella can carry out normal intracellular transport in other phagocytic and non-phagocytic cells.
Pathogenic Mechanism of Brucella Abortus
Brucella has virulence factors (such as exotoxins, cytolysins, endotoxins, lipopolysaccharides, and apoptosis inducers) that are not typical, but these virulence factors play a role in bacterial invasion of host cells, intracellular parasitism, and arrival of cells. Among them, the internal replication site – the rough endoplasmic reticulum (RER) is essential.