Viral-bacterial co-infections screen in vitro reveals molecular processes affecting pathogen proliferation and host cell viability.

Details

Serval ID
serval:BIB_9A754395BCC1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Viral-bacterial co-infections screen in vitro reveals molecular processes affecting pathogen proliferation and host cell viability.
Journal
Nature communications
Author(s)
Walch P., Broz P.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
04/10/2024
Peer-reviewed
Oui
Volume
15
Number
1
Pages
8595
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The broadening of accessible methodologies has enabled mechanistic insights into single-pathogen infections, yet the molecular mechanisms underlying co-infections remain largely elusive, despite their clinical frequency and relevance, generally exacerbating symptom severity and fatality. Here, we describe an unbiased in vitro screening of pairwise co-infections in a murine macrophage model, quantifying pathogen proliferation and host cell death in parallel over time. The screen revealed that the majority of interactions are antagonistic for both metrics, highlighting general patterns depending on the pathogen virulence strategy. We subsequently decipher two distinct molecular interaction points: Firstly, murine Adenovirus 3 modifies ASC-dependent inflammasome responses in murine macrophages, altering host cell death and cytokine production, thereby impacting secondary Salmonella infection. Secondly, murine Adenovirus 2 infection triggers upregulation of Mprip, a crucial mediator of phagocytosis, which in turn causes increased Yersinia uptake, specifically in virus pre-infected bone-marrow-derived macrophages. This work therefore encompasses both a first-of-its-kind systematic assessment of host-pathogen-pathogen interactions, and mechanistic insight into molecular mediators during co-infection.
Keywords
Animals, Coinfection/microbiology, Coinfection/virology, Mice, Macrophages/microbiology, Macrophages/virology, Macrophages/metabolism, Host-Pathogen Interactions, Inflammasomes/metabolism, Cell Survival, Mice, Inbred C57BL, Phagocytosis, Adenoviridae Infections/virology, Cytokines/metabolism, Salmonella Infections/microbiology, Salmonella Infections/immunology
Pubmed
Open Access
Yes
Create date
11/10/2024 15:01
Last modification date
11/10/2024 19:15
Usage data