Recent molecular insights into rickettsial pathogenesis and immunity

Abstract

Human infections with arthropod-borne Rickettsia species remain a major global health issue, causing significant morbidity and mortality. Epidemic typhus due to Rickettsia prowazekii has an established reputation as the 'scourge of armies', and as a major determinant of significant 'historical turning points'. No suitable vaccines for human use are currently available to prevent rickettsial diseases. The unique lifestyle features of rickettsiae include obligate intracellular parasitism, intracytoplasmic niche within the host cell, predilection for infection of microvascular endothelium in mammalian hosts, association with arthropods and the tendency for genomic reduction. The fundamental research in the field of Rickettsiology has witnessed significant recent progress in the areas of pathogen adhesion/invasion and host immune responses, as well as the genomics, proteomics, metabolomics, phylogenetics, motility and molecular manipulation of important rickettsial pathogens. The focus of this review article is to capture a snapshot of the latest developments pertaining to the mechanisms of rickettsial pathogenesis and immunity.

Figure 1. Signaling mechanisms underlying Rickettsia-induced transcriptional activation and potential pathogen-associated molecular patterns as the determinants of host cell response and fate

Potential interactions, in other words predictions that remain to be tested at this stage, are indicated by dotted lines. Since these have not yet been investigated, they are indicated by question marks. Solid lines indicate interactions/connections that are known and proven experimentally.