We are working on the identification, description, and treatment of congenital and acquired syndromes of increased susceptibility to infection primarily affecting the phagocytes, including those related to nontuberculous mycobacteria. These organisms are important pathogens only in the immunocompromised host, so we have sought to identify patients without recognized forms of immunocompromise who have these infections and then determine the nature of their susceptibility. In this way we can identify novel pathways involved in the control of mycobacteria and potentially other intracellular pathogens such as Salmonella. We have identified several discrete abnormalities in these patients, all of which center around macrophage/lymphocyte interactions leading to the production of interferon gamma. The study of these ?experiments of nature? highlights the critical role of the macrophage/ lymphocyte interaction in control of mycobacteria and has led to the development of novel therapies that may have important applications in the most deadly infectious disease, tuberculosis - Mycobacteria, Leukocyte adhesion deficiency, Granulomata, Treatment, Interferon gamma, Nontuberculous, Interferon gamma receptor 1 - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000647-08
Application #
6288907
Study Section
Special Emphasis Panel (LHD)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Xie, Yingda L; Rosen, Lindsey B; Sereti, Irini et al. (2016) Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFN? Autoantibodies. Clin Infect Dis 62:770-773
Spinner, Michael A; Ker, Jennifer P; Stoudenmire, Charles J et al. (2016) GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus-associated hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol 137:638-40
Uzel, Gulbu; Sampaio, Elizabeth P; Lawrence, Monica G et al. (2013) Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. J Allergy Clin Immunol 131:1611-23
Palmore, Tara N; Shea, Yvonne R; Conville, Patricia S et al. (2009) ""Mycobacterium tilburgii,"" a newly described, uncultivated opportunistic pathogen. J Clin Microbiol 47:1585-7
Zelazny, Adrian M; Root, Jeremy M; Shea, Yvonne R et al. (2009) Cohort study of molecular identification and typing of Mycobacterium abscessus, Mycobacterium massiliense, and Mycobacterium bolletii. J Clin Microbiol 47:1985-95
Sampaio, Elizabeth P; Elloumi, Houda Z; Zelazny, Adrian et al. (2008) Mycobacterium abscessus and M. avium trigger Toll-like receptor 2 and distinct cytokine response in human cells. Am J Respir Cell Mol Biol 39:431-9
Uzel, Gulbu; Tng, Emilia; Rosenzweig, Sergio D et al. (2008) Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1). Blood 111:209-18
Freeman, Alexandra F; Holland, Steven M (2008) The hyper-IgE syndromes. Immunol Allergy Clin North Am 28:277-91, viii
Elloumi, Houda Zghal; Holland, Steven M (2008) Complex regulation of human cathelicidin gene expression: novel splice variants and 5'UTR negative regulatory element. Mol Immunol 45:204-17
Holland, Steven M (2007) Interferon gamma, IL-12, IL-12R and STAT-1 immunodeficiency diseases: disorders of the interface of innate and adaptive immunity. Immunol Res 38:342-6

Showing the most recent 10 out of 66 publications