Host range	Ticks with a wide host range such as I. ricinus, are naturally exposed to a greater variety of pathogens compared to ticks with a narrow host range such as R. microplus (Estrada-Peña et al., 2015).
Number of hosts	The potential transmission of pathogens could be limited when considering the host contact rate of 1- and 2- host ticks vs. 3-host ticks. This effect may however be partially annulled by the phenomenon of transovarial passage, when pathogens are passaged from the female to her eggs and offspring, which can subsequently infect new hosts. Argasid ticks of which the nymphs and adults take several blood meals, have a high host contact rate and could theoretically acquire or transmit pathogens from and to multiple hosts.
Midgut infection and escape barrier	The pathogen needs to pass through the midgut to reach the salivary glands and be transmitted with tick saliva, and for migration of some pathogens to the ovaries to allow transovarial pathogen passage. Mechanisms to pass the midgut infection barrier may depend on the presence and structure of specific surface receptors, such as TROSPA, to which OspA from B. burgdorferi adheres, allowing the spirochete to colonize the midgut (Pal et al., 2004).
Innate immune response	Pathogens need to overcome tick defense mechanisms, such as the phagocytosis of microbes by hemocytes, antimicrobial peptides and RNA interference, in order to be transmitted with tick saliva (Hajdušek et al., 2013).
Salivary gland infection and escape barrier	Pathogens must cross into the salivary glands for transmission with saliva during feeding, but little is known about the molecular mechanisms behind this entry. Once inside the salivary glands, the pathogen has to be released into the saliva stream to be transmitted. For example, B. burgdorferi uses tick salivary gland proteins to facilitate infection of the mammalian host (Ramamoorthi et al., 2005).
Pathogen strains	Differences between pathogen strains to infect and be transmitted by ticks have been widely reported (e.g., Kleiboeker et al., 1999; de la Fuente et al., 2001).
Tick microbiome-pathogen interactions	Microbiome play an essential role in various aspects of the arthropods life cycle and there is an increasing interest to elucidate arthropod-microbiome interactions. Perturbation of the microbiome caused changes in the integrity of the peritrophic membrane and may affect pathogen infection (Narasimhan et al., 2014).
Cross-Immunity interference	Competition between microorganisms within the tick may affect vector competence. Ticks infected with one Rickettsia species were for instance refractory to transovarial passage of a second Rickettsia species (Macaluso et al., 2002).
Abiotic factors	Abiotic factors such as temperature and relative humidity not only have a direct effect on tick development, questing activity and longevity, but temperature may also modulate pathogen development and survival in ticks (Shih et al., 1995; Estrada-Peña et al., 2011).