The Wilson Laboratory

The mammalian immune system is extremely complex, consisting of both innate and adaptive constituents. The complex and varied nature of the immune system is necessary to effectively protect the host from the constant barrage of microbial assaults we all face on a daily basis. Our laboratory focuses on elucidating and understanding the role of chemokines in the immune system . Chemokines are small proteins shown to be involved in two distinctly different aspects of immunity. One function of chemokines is to help direct migrating immune cells to appropriate tissues. A second function of chemokines is to act as antimicrobial proteins (AMPs) which directly kill or inhibit microbes.

Specifically one aim of our laboratory is to understand how migrating antibody secreting cells accumulate in the appropriate tissue. Our previous work has shown that the chemokine CCL28 plays an indispensable role in directing the homing of IgA secreting B cells (IgA ASC) to the lactating mammary gland. Interestingly, although CCL28 plays a vital role for IgA ASC recruitment to the lactating mammary gland this chemokine apparently plays no role in the accumulation of T cells to the same tissue. This specificity of chemokine involvement in B cell vs. T cell homing to a specific tissue is an excellent illustration of the complex and intricate nature of lymphocyte homing to mucosal tissues. Currently our laboratory is working to understand, at the molecular level, what directs IgA ASC to specific mucosal tissues (especially exocrine glands). For mucosal vaccines to reach their full potential in disease prevention, it is imperative that we understand the molecular mechanisms of lymphocyte homing to mucosal tissues. This is particularly true if vaccines are to be designed in which a vaccine is administered via one mucosal surface but where antibody protection is also desirable at other mucosal sites.

The chemokine CCL28, in addition to mediating efficient migration of IgA antibody secreting cells to mucosal tissues, has also been shown to function as an AMP. Using CCL28 as a model antimicrobial chemokine we are studying the mechanisms by which bacteria defend themselves from the mammalian produced AMPs. Working with the laboratory of Dr. David Erickson we have developed a flow cytometry based assay to quantitate the ability of AMPs to bind and kill bacteria. Using this assay we have screed hundreds of mutant bacteria and identified several bacterial genes involved in protecting bacteria from the action of AMPs.

Both of these projects are funded through National Institutes of Health grants  through 2015.