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Published on: March 20, 2013
Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection
Jennifer A Philips1, Eric J Rubin, Norbert Perrimon
1Department of Genetics, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA. jphilips@partners.org
Abstract:
Certain pathogens, such as Mycobacterium tuberculosis, survive within the hostile intracellular environment of a macrophage. To identify host factors required for mycobacterial entry and survival within macrophages, we performed a genomewide RNA interference screen in Drosophila macrophage-like cells, using Mycobacterium fortuitum. We identified factors required for general phagocytosis, as well as those needed specifically for mycobacterial infection. One specific factor, Peste (Pes), is a CD36 family member required for uptake of mycobacteria, but not Escherichia coli or Staphylococcus aureus. Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity.
Insights
Researchers identified host factors crucial for mycobacterial entry and survival. A specific CD36 family member, Peste (Pes), mediates mycobacterial uptake, highlighting conserved roles for scavenger receptors in innate immunity.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Mycobacterium tuberculosis survives within macrophages, posing a significant challenge to host defense.
- Understanding host factors involved in pathogen entry and survival is critical for developing new therapeutic strategies.
Purpose of the Study:
- To identify host factors essential for mycobacterial entry and intracellular survival.
- To investigate the specific role of identified factors in the interaction between macrophages and mycobacteria.
Main Methods:
- A genomewide RNA interference screen was conducted in Drosophila macrophage-like cells.
- Mycobacterium fortuitum was used to screen for host factors involved in phagocytosis and infection.
Main Results:
- The screen identified factors required for general phagocytosis and those specifically important for mycobacterial infection.
- A CD36 family member, Peste (Pes), was found to be essential for mycobacterial uptake but not for other bacteria like E. coli or S. aureus.
- Mammalian class B scavenger receptors (SRs) facilitated bacterial uptake into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating M. fortuitum uptake.
Conclusions:
- The study reveals novel host factors, including Peste (Pes), that regulate mycobacterial interaction with host cells.
- Conserved roles for class B scavenger receptors in pattern recognition and innate immunity against mycobacteria are suggested.
- These findings provide insights into host-pathogen interactions and potential targets for anti-mycobacterial therapies.
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