Mucosal vaccines. The vast majority of pathogenic microorganisms infect susceptible hosts via mucosal barriers. Unfortunately, the majority of vaccines approved by the FDA do not induce mucosal immune responses and, therefore, cannot prevent microorganisms from entering across mucus membranes.  Vaccines that stimulate immune responses that are able to combat infectious agents at the sites of entry (mucosal surfaces) are most desirable because they provide an additional layer of adaptive immune protection.
    It was previously believed that mucosal immune responses can only be induced by antigens that are administered to mucosal membranes, while parenterally administered vaccines promote only serum immune responses. Over a decade ago, we discovered that subcutaneously administered vaccines containing the active form of vitamin D3 (calcitriol) could promote the induction of both systemic and mucosal immune responses. We characterized cellular mechanisms involved in the generation of mucosal immune responses following cutaneous vaccination with antigen plus calcitriol. It appears that subcutaneous immunization with calcitriol containing vaccines alters the migratory properties of antigen-laden dendritic cells and allows their localization into the classical inductive sites of mucosal immunity, Peyer’s patches.
    Currently, we study mechanisms by which natural molecules like TLR ligands can promote the generation of mucosal immunity and the role that calcitriol may play in these processes.
Immune senescence. It is well accepted that aged individuals exhibit compromised systemic and mucosal immune responses paralleled with dysregulation in cytokine production. We previously reported that excesses in the cellular oxidative stress and the associated redox imbalance could contribute significantly to declines in the immune competence of aged rodents. We have recently discovered that the lymphoid organs (e.g. peripheral lymph nodes, spleens and bone marrow) of aged mice contain increased numbers of Gr1+CD11b+ inhibitory macrophages. These cells are able to alter cytokine production and significantly suppress aged naïve T-cell proliferation via an NO-dependent mechanism. Gr1+CD11b+ cells are virtually absent in the lymphoid organs of mature adult animals. Other investigators reported that the numbers of Gr1+CD11b+ inhibitory macrophages are greatly increased following multiple pathologic conditions (e.g. bacterial and viral infections, polymicrobial sepsis, trauma or developing tumor). These cells play a dual role. On one hand, Gr1+CD11b+ cells aid the host in fighting microbial infection, but on the other hand, they can non-specifically suppress the host’s immune defenses. Our research interest in this area is to understand and correct the cause of increased numbers of Gr1+CD11b+ inhibitory macrophages in the lymphoid organs of aged animals.