Differences in francisella tularensis subsp. novicida infection competence in cell lines from a natural vector and non-vector tick species

Authors: REIF, KATHERINE - Kansas State University; Ujczo, Jessica; ALPERIN, DEBRA - Washington State University; Noh, Susan

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/13/2018
Publication Date: 8/23/2018
Citation: Reif, K.E., Ujczo, J.K., Alperin, D.C., Noh, S.M. 2018. Differences in francisella tularensis subsp. novicida infection competence in cell lines from a natural vector and non-vector tick species. Scientific Reports. 8(1):12685. https://doi.org/10.1038/s41598-018-30419-4.
DOI: https://doi.org/10.1038/s41598-018-30419-4

Interpretive Summary: Tick-borne diseases have a large negative impact on human and animal health. One of the major limitations in preventing these diseases is understanding vector competence, which is the ability of the tick to acquire, maintain, and transmit a pathogen. Some tick species, such as Ixodes scapularis and Dermacentor andersoni, can serve as competent vectors for multiple tick-borne pathogens, and some tick-borne pathogens can be successfully transmitted by multiple tick species. Vector competence for a given tick-borne pathogen can vary among different tick species and within populations of the same tick species. Moreover, vector competence can be influenced by numerous biotic and abiotic variables. Examples of biotic variables that can affect vector competence include the presence of host cell receptors for pathogen attachment and entry, accessibility to required nutrients, innate immune system that allows pathogen replication and, direct or indirect interaction with co-infecting microbiota. Examples of abiotic variables that can affect vector competence, and more broadly vectorial capacity, include temperature and humidity. In the United States, D. andersoni and D. variabilis are recognized vectors of Francisella while Ixodes scapularis, despite occurring in F. tularensis-endemic areas, is not. Using cell lines derived D. andersoni (DAE100) and I. scapularis (ISE6), we investigated if the ecological relevance of these tick species in the transmission of F. tularensis subsps. Was present at the cellular level. Overall we determined that the bacteria were better able to enter and replicated to higher levels in the cells from the natural vector. At ambient temperatures, similar to what a tick might experience when off the mammalian host, bacteria in the tick cells were maintained at higher levels for longer periods of time. Using these two cell types will help to identifying determinants of vector competence which is required to develop effective intervention and control strategies to prevent tick-borne diseases in humans and animals.

Technical Abstract: Dermacentor andersoni is a natural vector of Francisella tularensis subsps, while Ixodes scapularis is not, though the geographic distribution and host range of the pathogen and both tick species overlap. To examine if inherent cellular infection competence underpins these ecological differences, we evaluated the competence of D. andersoni (DAE100) and I. scapularis (ISE6) cell lines to support F. tularensis subsp. novicida (F. novicida) infection and replication. We hypothesized F. novicida would infect both tick cell lines, but that infection would be more productive in the cell line derived from D. andersoni than I. scapularis. Specifically, we investigated whether there were differences in F. novicida i) invasion, ii) replication, or iii) tick cell viability between DAE100 and ISE6 cells. We further examined the influence of temperature on infection kinetics. Both cell lines were permissive to F. novicida infection; however, there were significantly greater bacterial levels and host cell mortality in DAE100 compared to ISE6 cells. Infection at environmental temperatures prolonged bacteremia and reduced tick cell mortality in both cell lines. Identifying cellular determinants of vector competence, and more globally vectorial capacity, are essential in understanding tick-borne disease ecology and designing effective intervention strategies.