Ehrlichiosis pathophysiology

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Overview

The pathophysiological process of ehrlichiosis begins with the inoculation of the disease from a tick vector. Following inoculation ehrlichiae and anaplasmosis enter the circulatory system in an attempt to infect a target cell. The infectious agents will then enter the cell via a receptor-mediated endocytosis. This particular endocytosis process is facilitated by a glycophoshoinositol anchored receptor. Both the Ehrlichiae and Anaplasma complete their reproduction process within the host cell's endosome.Infectious agents of both disease are then able to reprogram a host cell's defense mechanisms in order to silently proliferate.

Pathogenisis

Pathogenisis of HME

• E. chaffeensis enter into the mononuclear phagocytes.
• Phagolysosome fusion is inhibited while host genes are suppressed and induced to enable intracellular replication.
• Cytokines IL-12 and IL-18 are downregulated in THP-1 cells.
• Genes that are responsible for upregulation of apoptosis such as SNAP 23, Rab5A and STX16 are downregulated in correlation to the downregulation of IL-12 and IL-18.
• E. chaffeensis secretes an immunoreactive ankyrin protein (200kDa) into the host's nucleus in an attempt to manipulate the gene regulation of the host cell.
• Other methods of E. chaffeensis include inhibiting the signal transduction pathway and circumventing host cell defense mechanisms.
• Organ failure and other pathogenic manifestations resulting in complications or death is a result of immune mediated pathology.

Pathogenisis of Human Granulocytotropic Anaplasmosis=

• A.phagocytophilum successfully resides within the host cells (PMN cells) cytoplasmic vacuoles.
• Apoptosis is suppressed due to the upregulation of bfl-1 and inhibiting anti-FAS. Both of which are responsible for inducing apoptosis within neutrophils.
• Host cell gene transcription is controlled through a secreted protein, AnkA, that travels into the host cell's nucleus.
• Research into the pathogensis of HGA has also shown upregulation of pro-inflammatory and IL-8 chemokines.
• The pathogenesis of HGA causes immunosuppression and thus fatality may be attributed to opportunistic pathogens.

Pathophysiology

General Tick Life Cycle

This image displays an example of the tick lifecycle, based on stages and the months that they are most likely to occur during.

• A tick's life cycle is composed of four stages: hatching (egg), nymph (six legged), nymph (eight legged), and an adult.
• Ticks require blood meal to survive through their life cycle.
• Hosts for tick blood meals include mammals, birds, reptiles, and amphibians. Ticks will most likely transfer between different hosts during the different stages of their life cycle.
• Humans are most often targeted during the nymph and adult stages of the life cycle.
• Life cycle is also dependent on seasonal variation.
• Ticks will go from eggs to larva during the summer months, infecting bird or rodent host during the larval stage.
• Larva will infect the host from the summer until the following spring, at which point they will progress into the nymph stage.
• During the nymph stage, a tick will most likely seek a mammal host (including humans).
• A nymph will remain with the selected host until the following fall at which point it will progress into an adult.
• As an adult, a tick will feed on a mammalian host. However unlike previous stages, ticks will prefer larger mammals over rodents.
• The average tick life cycle requires three years for completion.
• Different species will undergo certain variations within their individual life cycles.

Transmission

• Ehrlichia are transported between cells through the host cell filopodia during initial stages of infection, whereas, in the final stages of infection the pathogen ruptures the host cell membrane.
• Most of the symptoms of Ehrlichiosis can likely be ascribed to the immune dysfunction that it causes.
• Early in infection, production of TNF-alpha, a cellular product that promotes inflammation and immune response, is suppressed.
• Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.
• Late in infection, however, production of this substance can be upregulated by 30 fold, which is likely responsible for the "toxic shock-like" syndrome seen in some severe cases of ehrlichiosis.