Molecular events involved in cellular invasion by Ehrlichia chaffeensis

By Linda on Nov 7, 2009 in Infections

Vet Parasitol. 2009 Sep 19; [Epub ahead of print]

Molecular events involved in cellular invasion by Ehrlichia chaffeensis and
Anaplasma phagocytophilum.

Rikihisa Y.

Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio
State University, 1925 Coffey Road, Columbus, OH 43210, USA.

Ehrlichia chaffeensis and Anaplasma phagocytophilum are obligatory intracellular
bacteria that preferentially replicate inside leukocytes by utilizing biological
compounds and processes of these primary host defensive cells. These bacteria
incorporate cholesterol from the host for their survival. Upon interaction with
host monocytes and granulocytes, respectively, these bacteria usurp the lipid
raft domain containing GPI-anchored protein to induce a series of signaling
events that result in internalization of the bacteria. Monocytes and neutrophils
usually kill invading microorganisms by fusion of the phagosomes containing the
bacteria with granules containing both antimicrobial peptides and lysosomal
hydrolytic enzymes and/or through sequestering vital nutrients. However, E.
chaffeensis and A. phagocytophilum alter vesicular traffic to create a unique
intracellular membrane-bound compartment that allows their replication in
seclusion from lysosomal killing. These bacteria are quite sensitive to reactive
oxygen species (ROS), so in order to survive in host cells that are primary
mediators of ROS-induced killing, they inhibit activation of NADPH oxidase and
assembly of this enzyme in their inclusion compartments. Moreover, host
phagocyte activation and differentiation, apoptosis, and IFN-gamma signaling
pathways are inhibited by these bacteria. Through reductive evolution,
lipopolysaccharide and peptidoglycan that activate the innate immune response,
have been eliminated from these gram-negative bacteria at the genomic level.
Upon interaction with new host cells, bacterial genes encoding the Type IV
secretion apparatus and the two-component regulatory system are up-regulated to
sense and adapt to the host environment. Thus dynamic signal transduction events
concurrently proceed both in the host cells and in the invading E. chaffeensis
and A. phagocytophilum bacteria for successful establishment of intracellular
infection. Several bacterial surface-exposed proteins and porins are recently
identified. Further functional studies on Ehrlichia and Anaplasma effector or
ligand molecules and cognate host cell receptors will undoubtedly advance our
understanding of the complex interplay between obligatory intracellular
pathogens and their hosts. Such data can be applied towards treatment,
diagnosis, and control of ehrlichiosis and anaplasmosis.