Investigator: Jacques Banchereau, PhD

The effective host protection from microbes relies upon a concerted action of both antigen (Ag)-nonspecific innate immunity and Ag-specific adaptive immunity. The innate system includes; cells: dendritic cells (DCs) macrophages, granulocytes, NK cells, complement and interferons, and is characterized by the ability to rapidly recognize invariant molecular patterns shared by pathogens. This recognition is a crucial step in inducing effective immune responses.

The main mechanism by which microbial components augment immune responses is to stimulate APC, especially DCs to produce proinflammatory cytokines and signal the presence of "danger" to cells of the adaptive immune system. These activated DC subsequently initiate primary T cell responses and dictate the type of T cell-mediated effector function. Therefore, activation of the innate immune system components, including DC themselves, will increase host protection from microbes.

With this in mind, BIIR scientists have developed a program aimed to improve protection of humans against infectious agents, through manipulation of the DC system. This can be accomplished either; by increasing the pool of DCs using cytokines that mobilize/activate DCs (which we collectively call DC-poietins) and capitalizing on their role in; adaptive immunity that leads to immune memory, and; innate immunity that leads to prompt, albeit non-specific, pathogen elimination, or; by specifically targeting the DCs in vivo using engineered viral vectors, the "Select Vaccine".

Thus far, our data suggest that G-CSF, a cytokine utilized to increase polymorphonuclear cells in patients, partially protects mice from Anthrax.