Chapter 13 : Transmission and the Determinants of Transmission Efficiency

Tick-host-rickettsiae interaction. (A) Ticks secrete a number of antihemostatic and immunomodulatory substances into the bite site to increase blood flow and reduce immune activation to the tick during feeding. Rickettsiae are imbibed with the blood meal or transmitted to the host during this stage of the interaction. As rickettsiae enter the midgut lumen, they attach to the host cell (B) and induce phagocytosis so as to be enveloped in a vacuole that is rapidly degraded (C) to lie in direct contact with the cytoplasm. (D) Spotted fever group rickettsiae move between and within each host cell using actin tail polymerization. (E) Ticks respond to rickettsiae by mounting an innate immune response that involves antimicrobial peptide gene transcription. Recent work suggests that the rickettsial invasion process is limited by tick antimicrobial peptides. doi:10.1128/9781555817336.ch13.f1

Vectors of the Rickettsiales. (A) Ixodidae tick. (B) Oriental rat flea, X. cheopis. (C) Body louse, P. humanus humanus. (D) Trombiculid larval mite (chigger). (Images A, B, and C from the Centers for Disease Control and Prevention Public Health Image Library. Image A modified from CDC image 10865; image B modified from CDC image 4633; image C modified from CDC image 9208. Image D from Wikipedia Commons. Photo credit: Luc Viatour; www.lucnix.be.) doi:10.1128/9781555817336.ch13.f2

Sylvatic and zoonotic transmission. Rickettsiae are transmitted in sylvatic cycles that involve a vector, in this case a tick, and their mammalian, reptilian, or avian hosts. Humans are accidentally infected when they encroach into the habitat where the sylvatic cycle exists. The cycle begins (1) and ends (4) when infected and uninfected ticks feed on large mammals. Horizontal transmission between infected and uninfected ticks can occur at this stage through cofeeding. Uninfected adults can also contract the pathogen by feeding on infected large mammals. If the bacterium is transmitted vertically (transovarial transmission), the egg clutch will be infected. Otherwise, uninfected egg masses will be oviposited. If transovarial transmission occurs, infected larvae will perpetuate pathogen transmission by feeding on small to medium-size hosts (2). Uninfected larvae can become infected at step 2 through cofeeding with infected larvae or by feeding on infected hosts. Infected larvae can also feed on humans (Z1), representing the first point where humans can be infected. Transmission continues to uninfected hosts and ticks in the same manner at stage 3, perpetuating the pathogen in nature. Human infection can occur at Z2 and Z3. Solid gray curved arrows follow the sylvatic cycle. The gray-to-white gradient curved arrows indicate accidental human infection. Solid gray straight arrows denote the infected path, while the open straight arrow denotes the uninfected path. (Portions of this figure adapted from images from the Centers for Disease Control and Prevention Public Health Image Library. Ticks modified from CDC image 6005; human modified from CDC image 3425; small mammals modified from CDC image 3381; large mammals modified from CDC image 3392.) doi: 10.1128/9781555817336.ch13.f3

Endosymbiotic rickettsial modulation of tick immune activation. Endosymbiotic rickettsiae like R. peacockii may recalibrate immune homeostatic norms, thereby increasing the sensitivity of ticks to secondary rickettsial infection. Primary rickettsial infections may increase the immunological sensitivity of ticks to secondary rickettsial infections. Although this hypothesis has not been tested, it is possible that by-products of replication like free peptidoglycan functionally saturate recognition proteins such as PGRP-LB, which normally prevents activation by degrading immunostimulatory peptidoglycan. Alternatively, rickettsiae may modulate host gene transcription or posttranslational modification of immune effectors to make them more potent. We hypothesize that endosymbiotic rickettsiae effectively lower the activation threshold (B) or increase basal homeostatic immune activity, bringing it closer to the activation threshold (C). Scenario A represents immune activation in ticks that possess no infection. Scenario D represents the immune activation that occurs when ticks possess a primary endosymbiont and imbibe a secondary rickettsia. We hypothesize that rapid and possibly sustained immune activation in scenario D limits infection of the ovary by a second rickettsia. Dashed lines represent immune activation threshold; solid lines represent baseline (constitutive) immune activity. doi:10.1128/9781555817336.ch13.f4