M.tb Killing by Macrophage Innate Immune Mechanisms: A Dissertation
Authors
Hartman, Michelle LFaculty Advisor
Hardy Kornfeld, M.D.Academic Program
Immunology and MicrobiologyUMass Chan Affiliations
MedicineDocument Type
Doctoral DissertationPublication Date
2011-09-07Keywords
Mycobacterium tuberculosisImmunity
Innate
Macrophages
Interleukin-1
Amino Acids, Peptides, and Proteins
Bacteria
Bacterial Infections and Mycoses
Biological Factors
Cells
Hemic and Immune Systems
Immunology and Infectious Disease
Microbiology
Metadata
Show full item recordAbstract
Macrophages infected with a heavy burden of M.tb Erdman undergo a cell death that initially resembles apoptosis but quickly transitions to necrosis. Unlike the previously reported TNF dependent apoptosis induced by avirulent Mycobacterium [1], this form of macrophage cell death is not microbicidal [2]. Microbicidal effects are observed however, when the heavily infected macrophage encounters an uninfected naïve macrophage. My studies describe in part, the crosstalk between the uninfected and infected macrophage that results in the killing of the intracellular M.tb Cell contact between the two cell populations is not necessary for this killing of bacilli to occur and the soluble “signal” of communication between the two cell populations is transferrable, without naïve macrophages present, to newly infected cells also resulting in the reduced viability of the bacilli. We have found that when the IL-1 receptor is absent in the naïve macrophage population that the co-culture antimycobacterial effect is abrogated, suggesting that IL-1 released by the infected dying macrophage is critical for naïve macrophages to respond in a way that results in the decrease in mycobacterial viability. The signaling between the two cell population ultimately converges on activation of iNOS in the infected cell however ROS appears not to be involved.DOI
10.13028/8kch-xp86Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31953Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/8kch-xp86