My research is in tuberculosis, cytokines, antigen processing, anti-microbial immunity, HIV-1, and pulmonary host defense.
T cells play a critical role in the immune response to the intracellular pathogen M. tuberculosis, which is estimated to infect one third of the world's population. T cells regulate the acquired immune response which controls primary infection and provide protection against exogenous reinfection. CD4+ T cells traditionally have been considered the main T cell subset responsible for regulating protective immune responses to M. tuberculosis. However, in addition to the CD4+ T cell, both gamma-delta T cell receptor bearing T cells (gamma delta cells) and CD8+ T cells have a role in protective immunity to M. tuberculosis. The study of CD4+, CD8+ and gamma delta T cell responses to M. tuberculosis is the main interest of my laboratory.
The focus is on characterization of mycobacterial antigens recognized by CD4+ and gamma-delta T cells, the role of cytokines such as IL-2, IL-12, IFN-gamma, IL-10 and TGF-beta in modulating the T cell responses to M. tuberculosis, the functional interaction of antigen-specific T cells with macrophages infected with mycobacteria, and the mechanisms used by M. tuberculosis infected macrophages to process and present antigens from the phagosome to the cell surface to these different T cell subsets. Recent studies have focused on identifying molecules of M. tuberculosis that interfere with MHC-II antigen processing. Specifically the role of mycobacterial lipoproteins and TLR receptors in regulating MHC-II antigen processing has become a major focus.
These studies use cellular immunological and cell biologic approaches to study the biology of M. tuberculosis infected macrophages and T cells. In addition, a murine in vivo model of M. tuberculosis infection of the lung is used to study the unique micro-environment where M. tuberculosis infection occurs and immune responses are initiated.
Pecora ND, Fulton SA, Reba SM, Simmons DP, Nagy N, Boom WH**, Harding CV**. Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection. Cellular Immunology, in press. (**Joint Senior Authorship)
Boom WH. New TB vaccines: is there a requirement for CD8+ T cells? (Editorial) J. Clin. Invest. 117:2092-2094, 2007. [PubMed]
Pennini ME, Yang J, Croninger CM, Boom WH, Harding CV. C/EBP* binds to CIITA promoters and inhibits CIITA expression in response to M. tuberculosis 19-kDa lipoprotein. J Immunology, 179:6910-8, 2007.
Stein CM, Zalwango S, Chiunda AB, Millard C, Leontiev DV, Horvath AL, Cartier KC, Chervenak K, Boom WH, Elston RC, Mugerwa RD, Whalen CC, Iyengar SK. Linkage and association analysis of candidate genes for TB and TNF-alpha| cytokine expression: Evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes. Human Genetics, 121:663-73, 2007.
Anis MM, Fulton S, Reba SM, Harding CV, Boom WH. Modulation of naïve CD4+ T cell responses to an airway antigen during pulmonary mycobacterial infection. Infection and Immunity, 75: 2260-8, 2007. PMCID: PMC1865791
Rojas RE, Thomas J, Gehring AJ, Hill P, Belisle J, Harding CV**, Boom WH**. Phosphatidylinositol mannoside from Mycobacterium tuberculosis binds alpha5beta1 integrin (VLA-5) on CD4+ T cells and induces adhesion to fibronectin. J. of Immunol. 177:2959-68, 2006. (**Joint Senior Authorship)
Pecora ND, Gehring AJ, Canaday DH, Boom WH**, Harding CV**. M. tuberculosis LprA Is a Lipoprotein Agonist of TLR2 That Regulates Innate Immunity and APC Function. J Immunol. 177:422-9, 2006. (**Joint Senior Authorship)