Activation of the innate immune system can enhance resistance to a variety of bacterial and viral infections. In
situations where the etiological agent of disease is unknown, such as a bioterror attack, stimulation of innate immunity
may be particularly useful as induced immune responses are often capable of providing protection against a broad range
of pathogens. In particular, the threat of an intentional release of a highly virulent bacterial pathogen that is either intrinsically
resistant to antibiotics, or has been weaponized via the introduction of antibiotic resistance, makes immunopotentiation
an attractive complementary or alternative strategy to enhance resistance to bacterial biothreat agents. Francisella tularensis,
Yersinia pestis, Bacillus anthracis, and Burkholderia mallei or pseudomallei can all be easily disseminated via
the respiratory route and infections can result in high mortality rates. Therefore, there has been a marked increase in research
on immunotherapeutics against these Tier 1 select agents over the last 10 years that will be covered in this review.
In addition, immunopotentiation against non-Tier 1 select agents such as Brucella spp., and Coxiella burnetii has also
been studied and will be reviewed here. In particular, we will focus on cellular targets, such as toll-like receptors (TLRs),
carbohydrate receptors and cytokine receptors, which have been exploited by immunomodulatory regimens that confer
broad-spectrum protection against virulent bacterial pathogens.