An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.
JoAnne L. Flynn,John Chan,Karla J. Triebold,Dyana K. Dalton,Timothy A. Stewart,Barry R. Bloom +5 more
TLDR
Gko mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFNs, and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN.Abstract:
Tuberculosis, a major health problem in developing countries, has reemerged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and many experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis, although they develop granulomas, gko mice fail to produce reactive nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma.read more
Citations
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Journal ArticleDOI
Immunology of tuberculosis.
JoAnne L. Flynn,John W. Y. Chan +1 more
TL;DR: This review summarizes the current understanding of the host immune response, with emphasis on the roles of macrophages, T cells, and the cytokine/chemokine network in engendering protective immunity.
Journal ArticleDOI
Disseminated tuberculosis in interferon gamma gene-disrupted mice.
Andrea M. Cooper,Dyana K. Dalton,Timothy A. Stewart,J P Griffin,David G. Russell,Ian M. Orme +5 more
TL;DR: It is shown that mice in which the IFN-gamma gene has been disrupted were unable to contain or control a normally sublethal dose of M. tuberculosis, delivered either intravenously or aerogenically, and that despite the lack of protective immunity, some DTH-like reactivity could still be elicited.
Journal ArticleDOI
Tumor necrosis factor-α is required in the protective immune response against mycobacterium tuberculosis in mice
JoAnne L. Flynn,Marsha M. Goldstein,John Chan,Karla J. Triebold,Klaus Pfeffer,Charles J. Lowenstein,Robert Schrelber,Tak W. Mak,Barry R. Bloom +8 more
TL;DR: The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection.
Journal ArticleDOI
T-cell quality in memory and protection: implications for vaccine design
TL;DR: The importance of using multiparameter flow cytometry to better understand the functional capacity of effector and memory T-cell responses, thereby enabling the development of preventative and therapeutic vaccine strategies for infections is highlighted.
Journal ArticleDOI
Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens
Carl Nathan,Michael U. Shiloh +1 more
TL;DR: This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity and identifies candidates for RNI-resistance genes in Mycobacterium tuberculosis and other pathogens.
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