kiny
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http://www.frontiersin.org/Cellular_and_Infection_Microbiology_-_closed_section/10.3389/fmicb.2012.00215/full
Infection of primary bovine macrophages with Mycobacterium avium subspecies paratuberculosis suppresses host cell apoptosis
Edward Kabara and Paul M. Coussens
Department of Biochemistry, Center for Animal Functional Genomics, Michigan State University, East Lansing, MI, USA
Department of Animal Science, Center for Animal Functional Genomics, Michigan State University, East Lansing, MI, USA
Introduction
Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease, is found in over 68% of cattle herds in the United States. The largest percentage of these animals are subclinically infected with the bacterium (USDA–APHIS–VS–CEAH, 2008). Johne’s disease costs the U.S. dairy industry up to $1.5 billion per year in loses (Jones, 1989). A controversial but developing link between MAP and some cases of human Crohn’s disease suggests that MAP may become a significant food safety concern (Spickler, 2006).
One of the key factors that makes MAP such an elusive pathogen is its ability to survive inside host macrophages. Typically, macrophages phagocytose and destroy microorganisms in the host. MAP, however, is able to prevent normal phagosome maturation allowing the bacteria to survive in stalled phagosomes, which become reservoirs for further bacterial growth (Hostetter et al., 2003; Tanaka et al., 2005). To better understand the nature of the host-pathogen interaction in infected macrophages, our group performed a large-scale microarray experiment to study the changes in relative expression of hundreds of host genes in MAP-infected cells. From the genes and pathways found to have altered expression, it was apparent that host cell apoptosis was an important area of focus (Kabara et al., 2010).
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Conclusion
Apoptosis of MAP-infected macrophages is important for the effective clearance of the bacterium from the host. However, our data demonstrates that MAP-infected macrophage populations contain a lower percentage of spontaneously apoptotic cells than uninfected cell populations in the same culture. Furthermore, these cells are much less likely to undergo apoptosis even after strong induction from agents such as H2O2. MAP-infected macrophages also show a drastically lower ability to activate caspases and contain lower caspase 3, 7, and 8 mRNA levels, which could be an explanation for the reduction in the ability of infected cells to enter apoptosis, relative to bystander macrophages, and cells from uninfected control cultures. Future work focused on the bacteria driven host apoptotic regulation may result in new treatments and vaccine candidates for Johne’s disease.
© 2012 Kabara and Coussens. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics
http://www.frontiersin.org/Cellular_and_Infection_Microbiology_-_closed_section/10.3389/fmicb.2012.00215/full
Infection of primary bovine macrophages with Mycobacterium avium subspecies paratuberculosis suppresses host cell apoptosis
Edward Kabara and Paul M. Coussens
Department of Biochemistry, Center for Animal Functional Genomics, Michigan State University, East Lansing, MI, USA
Department of Animal Science, Center for Animal Functional Genomics, Michigan State University, East Lansing, MI, USA
Introduction
Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease, is found in over 68% of cattle herds in the United States. The largest percentage of these animals are subclinically infected with the bacterium (USDA–APHIS–VS–CEAH, 2008). Johne’s disease costs the U.S. dairy industry up to $1.5 billion per year in loses (Jones, 1989). A controversial but developing link between MAP and some cases of human Crohn’s disease suggests that MAP may become a significant food safety concern (Spickler, 2006).
One of the key factors that makes MAP such an elusive pathogen is its ability to survive inside host macrophages. Typically, macrophages phagocytose and destroy microorganisms in the host. MAP, however, is able to prevent normal phagosome maturation allowing the bacteria to survive in stalled phagosomes, which become reservoirs for further bacterial growth (Hostetter et al., 2003; Tanaka et al., 2005). To better understand the nature of the host-pathogen interaction in infected macrophages, our group performed a large-scale microarray experiment to study the changes in relative expression of hundreds of host genes in MAP-infected cells. From the genes and pathways found to have altered expression, it was apparent that host cell apoptosis was an important area of focus (Kabara et al., 2010).
.
.
.
.full article in link
.
.
.
Conclusion
Apoptosis of MAP-infected macrophages is important for the effective clearance of the bacterium from the host. However, our data demonstrates that MAP-infected macrophage populations contain a lower percentage of spontaneously apoptotic cells than uninfected cell populations in the same culture. Furthermore, these cells are much less likely to undergo apoptosis even after strong induction from agents such as H2O2. MAP-infected macrophages also show a drastically lower ability to activate caspases and contain lower caspase 3, 7, and 8 mRNA levels, which could be an explanation for the reduction in the ability of infected cells to enter apoptosis, relative to bystander macrophages, and cells from uninfected control cultures. Future work focused on the bacteria driven host apoptotic regulation may result in new treatments and vaccine candidates for Johne’s disease.
© 2012 Kabara and Coussens. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics
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