I study the signals necessary for proper dendritic cell function and maturation.

As of 2000, it was estimated that over 2 billion people in the world were infected with Mycobacterium tuberculosis (Mtb) while more than 2 million people die from it each year. Despite these numbers there are limitations in the treatment of Mtb. Typically, Mtb infects macrophages, which upon encounter with the pathogen mount an inflammatory response. This response recruits other leukocytes including dendritic cells and T lymphocytes that then form a granuloma to contain and control infection. The mechanisms behind control and containment by the adaptive immune system are not well understood. The long-term goal of this project is to determine the immunological mechanisms used by the adaptive immune system that could then provide groundwork for new therapeutic medicines and vaccines. Recently, our lab demonstrated that a calcium-calmodulin (CaM)-Kinase II (CaM K II) pathway is inhibited by virulent Mtb and that this inhibiton contributes to incomplete phagosomal maturation and the bacilli’s intracellular survival in macrophages. Important gaps in our knowledge include: (1) Does CaM K II regulate phagosomal maturation and antigen presentation in dendritic cells and 92) if the CaM K II pathway is also inhibited by Mtb in dendritic cells to prevent MHC class II antigen presentation and evade the adaptive immune system. Based on our preliminary data, the hypotheses are: (a) CaM K II pathway is a general regulator of phagosomal maturation in macrophages and dendritic cells, (b) CaM K II regulates the trafficking of MHC class II molecules , and (c) Mtb-induced inhibition of this pathway contributes to defective antigen presentation

Herrmann TL, Agrawal RS, Connolly SF, McCaffrey RL, Schlomann J, Kusner DJ. MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II. J Leukoc Biol. 2007 Sep;82(3):686-99. Epub 2007 Jun 22. PubMed PMID: 17586661.

Herrmann TL, Morita CT, Lee K, Kusner DJ. Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells. J Leukoc Biol. 2005 Dec;78(6):1397-407. Epub 2005 Oct 4. PubMed PMID: 16204647.