single gene, and because they can use imaging to track the progression of infection and cellular trafficking in real time.

In this chapter, six scientists presented the state of the science regarding the pathogenesis of tick-borne infections—specifically those caused by pathogens in the Anaplasma, Borrelia, Ehrlichia, and Rickettsia genera.

PATHOGENESIS OF BORRELIA BURGDORFERI INFECTION AND DISEASE

Janis J. Weis, Ph.D., Department of Pathology, University of Utah School of Medicine


In humans, the bite of the infected tick is required for introduction of the pathogen through healthy skin. This extracellular pathogen starts in the dermal tissue where it begins to adapt to life in the mammalian host by changing the expression of its surface glycoproteins. At the same time, the bacterium stimulates responses of inflammatory cells and their secreted mediators that cause acute-phase lesions such as the classical erythema migrans (EM) lesion. The bacterium also activates proteases and other induced host cell molecules to allow for dissemination through the blood and into other tissues, including secondary skin lesions, joints, the heart, and nervous tissue (Coleman et al., 1997; Gebbia et al., 2004; Rosa et al., 2005).

Differences in the severity and spectrum of disease among patients infected with Borrelia burgdorferi is one of the hallmarks of Lyme disease (Steere and Glickstein, 2004). The reasons for this variation include both genetic differences among strains of the bacterium and differences in the host responses. On the bacterial side, genetically distinct strains, identified by ribosomal spacer types and outer surface protein C (OspC) heterogeneity, have been associated with invasive versus localized cutaneous disease (Wang et al., 2002; Wormser et al., 2008a). Furthermore, B. burgdorferi is characterized by a large and complex plasmid content, some of which are essential for infection and others which can vary among strains (Rosa et al., 2005). Similarly, the host response has significant differences in the host response. Among human patients, approximately 60 percent of infected patients who do not receive early treatment develop clinical arthritis (Steere et al., 1987). This difference between those patients who do and those who do not develop arthritis reflects, at least in part, genetic differences in host response. These effects can be studied using inbred strains of mice with defined genetic differences and with clearly reproducible difference in the severity of carditis and arthritis following B. burgdorferi infection (Barthold et al., 1990).

The use of gene knockout mice has begun to unravel the genetic contribution to the spectrum of the disease. Severely combined immunodeficient C3H/HeJ mice (SCID)—which lack B and T lymphocytes—develop severe



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