Francisella tularensis- Immune Cell Activator, Suppressor, or Stealthy Evader: The Evolving View from the Petri Dish.
One of the hallmarks of pulmonary tularemia, which results from inhalation ofFrancisella tularensis- a significant bioterrorism concern, is the lack of an acute TH1-biased inflammatory response in the early phase of disease (days 1-3) despite significant bacterial loads. In an effort to understand this apparent hypo-responsiveness, many laboratories have utilizedin vitrocell-based models as tools to probe the nature and consequences of host cell interactions withF. tularensis. The first uses of this model suggested that mammalian host cells recognize this bacterium principally through TLR2 to evoke a robust, classical TH1-biased cytokine response including TNF, IL-6, IL-1β, and IFN-γ. Others used this model in concert with a variety of non-genetic perturbations of the bacterial-host cell interaction and suggested thatF. tularensisactively-suppressed the cellular response. Consistent with this notion, others engaged this model to assess isogenic mutants and, in many cases, found the mutant bacteria to be more pro-inflammatory than their WT counter-parts. Frequently, these observations were interpreted as evidence for the immunosuppressive function of the gene of interest. However, recently appreciated roles of the health of the bacterium and the impact of host factors have refined this model to suggest a "stealthy" mode of bacterial-host cell interaction (rather than one involving active suppression) consistent with the observations during early phase disease.
Center for Immunology & Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Kristen M
KM
Holland
Center for Immunology & Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Sarah J
SJ
Rosa
Center for Immunology & Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Karsten R O
KR
Hazlett
Active suppression; Cytokines; Host-adaptation; Host-response; Tularemia
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