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    HIV promotes the intracellular survival of an invasive strain of Salmonella Typhimurium in macrophages

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    A study of Florence Niedergang team

    HIV promotes the intracellular survival of an invasive strain of Salmonella in macrophages

     

    Florence Niedergang's lab shows that HIV-1 infection of macrophages allows an invasive strain of Salmonella enterica Typhimurium, which has developed in sub-Saharan Africa, to survive better in macrophages. This better survival is not directly linked to a physical connection between the viral compartment and the vacuole of the bacteria inside the cells. This study is published in the journal Biol. Cell.

    Human Immunodeficiency Virus Type 1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome, or AIDS, characterized by a deficiency in the immune system leading to vulnerability to opportunistic infections.  According to WHO, approximately 38 million people worldwide are living with HIV, still causing more than 700,000 deaths in 2018. The pandemic particularly affects sub-Saharan Africa where many superinfections are developing as bacterial infections with non-typical strains of Salmonella enterica. These strains, such as Salmonella Typhimurium, generally cause well-controlled gastroenteritis in healthy individuals. However, in immunocompromised individuals, invasive non-typhoidal strains have been detected, leading to severe systemic infection, causing nearly 400,000 deaths annually. The specific development of these invasive strains of Salmonella Typhimurium in HIV-1 infected patients is not yet well understood.

     

    Macrophages play a major role in the elimination of pathogenic bacteria by phagocytosis. However, macrophages are permissive to HIV-1 infection and constitute one of the cellular reservoirs for the virus. When infected with HIV-1, they show defects in phagocytosis and bacterial clearance.

    In this study, macrophages previously infected with HIV-1 were shown to have defects in the elimination of Salmonella Typhimurium, even more pronounced for a non-typhoidal invasive strain of Salmonella, ST313. The authors investigated whether these invasive bacteria could hijack the viral compartment to their advantage to better survive in macrophages. Living cells infected with a fluorescent virus were observed under the confocal microscope of the IMAG'IC platform located in the L3 containment laboratory and then by FIB-SEM (FIB-SEM) at the University of Lausanne. Thanks to a 3D reconstruction, the authors showed that the compartments formed by the two pathogens are not directly connected in the co-infected cells.

    Legend: 3D analysis by confocal and electron microscopy showed that Salmonella Typhimurium ST313 bacteria (in pink) do not directly hijack the HIV-1 compartment (in green) to better survive in macrophages. Nuclei in blue.

     

     

     Thus, the invasive bacteria Salmonella Typhimurium ST313 survive better in macrophages than non-invasive bacteria. They do not directly take advantage of the niche created by the viral compartment, but exploit a globally modified cell host that is currently being caracterized.

     

     

     Drawing by Isabelle Bury and Gabrielle Lê-Bury, showing the separation between the compartments containing viruses and bacteria in macrophages. © Gabrielle Lê-Bury

     

     

     

     

     

     

     

     

     

     

    Study performed in collaboration with Caroline Kizilyaprak and Bruno Humbel (Lausanne University) as well as Melita Gordon and Jay Hinton (Liverpool University) with the support of ANRS.

     

    Reference

    Lê‐Bury G., Deschamps C., Kizilyaprak C., Blanchard W., Daraspe J., Dumas A., Gordon M., Hinton J., Humbel B. and Niedergang F. (2020), Increased intracellular survival of Salmonella Typhimurium ST313 in HIV‐1‐infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment. Biol. Cell, 112: 92-101. doi:10.1111/boc.201900055

     

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