What Can Go Wrong When Applying Immune Modulation Therapies to Target Persistent Bacterial Infections

Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity. Often, the causative agents of persistent infections are not drug-resistant species. Instead, bacterial persister cells temporarily enter a physiological state that is refractory to different classes of antibiotics. Supplemental therapies that potentiate antibiotic bactericidal efficiency and/or immune clearance of persistent pathogenic species may greatly improve the outcome of infectious disease. Here, we discuss the various outcomes in experimental studies in which a mega-dose of the energy-boosting vitamin B3 (nicotinamide) was applied in murine models of chronic infection to stimulate immune clearance of chronic infection or as an immune prophylactic treatment against the highly infectious pathogen, Burkholderia pseudomallei. It is our intent to raise awareness of the risks associated with immune modulation therapies. There is great variance in host immune responses to pathogenic bacteria. Each immune modulation approach needs to be tailored to a well-characterized host-pathogen interaction.